42 results on '"Cravero E"'
Search Results
2. (822) - Routine vs. Selective Distal Perfusion Catheter Use in Veno-Arterial Extracorporeal Membrane Oxygenation?
- Author
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Cravero, E., Stanberry, L., Eckman, P.M., and Hryniewicz, K.
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- 2024
- Full Text
- View/download PDF
3. Genes and atherosclerosis: at the origin of the predisposition
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PUDDU, P., CRAVERO, E., PUDDU, G. M., and MUSCARI, A.
- Published
- 2005
4. (822) - Routine vs. Selective Distal Perfusion Catheter Use in Veno-Arterial Extracorporeal Membrane Oxygenation?
- Author
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Buda, K.G., Cravero, E., Stanberry, L., Eckman, P.M., and Hryniewicz, K.
- Subjects
- *
EXTRACORPOREAL membrane oxygenation , *PERFUSION , *CATHETERS - Published
- 2024
- Full Text
- View/download PDF
5. The functional role of dendritic cells in atherogenesis
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Puddu P., Puddu G. M., Cravero E., MUSCARI, SILVIA, MUSCARI, ANTONIO, Puddu P., Puddu G.M., Cravero E., Muscari S., and Muscari A.
- Published
- 2010
6. Evidenze geologiche di variazioni climatico-ambientali cicliche avvenute nel periodo storico nel Salento (Puglia)
- Author
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CONTE M., CRAVERO E., ORTOLANI F., PAGLIUCA S., VECCHIONE C., PENNETTA, MICLA, Centro Universitario Europeo per i Beni Culturali, Conte, M., Cravero, E., Ortolani, F., Pagliuca, S., Pennetta, Micla, and Vecchione, C.
- Published
- 1996
7. The genetic basis of essential hypertension
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PUDDU, P., primary, PUDDU, G.M., additional, CRAVERO, E., additional, FERRARI, E., additional, and MUSCARI, A., additional
- Published
- 2007
- Full Text
- View/download PDF
8. The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis
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De Pascalis Susanna, Cravero Eleonora, Puddu Giovanni M, Puddu Paolo, and Muscari Antonio
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Medicine - Abstract
Abstract An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
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- 2009
- Full Text
- View/download PDF
9. Gene-Based Therapy for Hypertension – Do Preclinical Data Suggest a Promising Future?
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Paolo Emilio Puddu, Eleonora Ferrari, Antonio Muscari, Giovanni M. Puddu, Eleonora Cravero, Puddu G.M., Cravero E., Ferrari E., Muscari A., and Puddu P.
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Male ,SENSE ,Genetic enhancement ,Genetic Vectors ,Bioinformatics ,Sensitivity and Specificity ,GENE VECTORS ,Renin-Angiotensin System ,Mice ,Risk Factors ,Rats, Inbred SHR ,Sense (molecular biology) ,Animals ,Humans ,Medicine ,Pharmacology (medical) ,RNA, Small Interfering ,Gene ,GENE THERAPHY ,business.industry ,Gene Transfer Techniques ,Genetic Therapy ,Oligonucleotides, Antisense ,Preclinical data ,Virology ,Rats ,Disease Models, Animal ,Blood pressure ,Hypertension ,Female ,Cardiology and Cardiovascular Medicine ,business ,ANTISENSE ,Forecasting - Abstract
Many experimental studies have obtained a prolonged control of blood pressure through gene treatment. This consists in the administration of genes coding for vasodilator proteins (the ‘sense’ approach), or of nucleotide sequences that are complementary to the mRNA of vasoconstrictor proteins, which are consequently synthesized in smaller amounts (the ‘antisense’ approach). Examples of the sense approach include the genes encoding endothelial nitric oxide synthase and kallikrein. Examples of the second type of approach are the antisense oligodeoxynucleotides to angiotensin-converting enzyme and endothelin-1. Also, RNA molecules, such as ribozymes and small interfering RNAs, are capable to inhibit RNA function. Whole sense genes are usually administered through viral vectors, while antisense oligonucleotides may be administered with plasmids or liposomes. Both viral and non-viral vectors have advantages and disadvantages. Despite the still persisting limitations, the possibility exists that in the future some forms of genetic treatment will be extended to the clinical setting, allowing a prolonged control of essential hypertension and its end-organ sequelae.
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- 2006
10. The relationships among hyperuricemia, endothelial dysfunction, and cardiovascular diseases: Molecular mechanisms and clinical implications
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Luca Vizioli, Eleonora Cravero, Antonio Muscari, Paolo Emilio Puddu, Giovanni M. Puddu, PUDDU P., PUDDU G.M., CRAVERO E., VIZIOLI L., and MUSCARI A.
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medicine.medical_specialty ,Antioxidant ,Endothelium ,Xanthine oxidoreductase ,Xanthine Dehydrogenase ,medicine.medical_treatment ,Allopurinol ,Oxypurinol ,Hyperuricemia ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,Internal medicine ,CARDIOVASCULAR RISK FACTORS ,medicine ,Humans ,Molecular Targeted Therapy ,Endothelial dysfunction ,business.industry ,medicine.disease ,Xanthine ,Atherosclerosis ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Risk factors ,Cardiovascular Diseases ,Oxidative stress ,Uric acid ,Endothelium, Vascular ,business ,Reactive Oxygen Species ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
SummaryUric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed.
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- 2012
11. The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases
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Silvia Muscari, Paolo Emilio Puddu, Giovanni M. Puddu, Eleonora Cravero, Antonio Muscari, Puddu P., Puddu G.M., Cravero E., Muscari S., and Muscari A.
- Subjects
Blood Platelets ,Monocyte chemotaxis ,Endothelium ,Platelet Aggregation ,medicine.medical_treatment ,Inflammation ,Prostacyclin ,Review ,Pharmacology ,Nitric oxide ,chemistry.chemical_compound ,Tissue factor ,Cell-Derived Microparticles ,Medicine ,Humans ,Platelet ,Blood Coagulation ,business.industry ,Cell Membrane ,nutritional and metabolic diseases ,Cytokine ,medicine.anatomical_structure ,chemistry ,Cardiovascular Diseases ,Immunology ,Endothelium, Vascular ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Microparticles (MPs) are small vesicles, ranging in size from 0.1 microm to 2 microm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.
- Published
- 2010
12. The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis
- Author
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Susanna De Pascalis, Eleonora Cravero, Paolo Emilio Puddu, Giovanni M. Puddu, Antonio Muscari, PUDDU P., PUDDU G.M., CRAVERO E., DE PASCALIS S., and MUSCARI A.
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medicine.medical_specialty ,Mitochondrial DNA ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,lcsh:Medicine ,Review ,Mitochondrion ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,Antioxidants ,Nitric oxide ,chemistry.chemical_compound ,Insulin resistance ,Risk Factors ,Internal medicine ,Diabetes Mellitus ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Endothelial dysfunction ,Molecular Biology ,Dyslipidemias ,Biochemistry, medical ,chemistry.chemical_classification ,Reactive oxygen species ,Macrophages ,Biochemistry (medical) ,lcsh:R ,Endothelial Cells ,Type 2 Diabetes Mellitus ,Cell Biology ,General Medicine ,Atherosclerosis ,medicine.disease ,Mitochondria ,Oxidative Stress ,Endocrinology ,chemistry ,Cardiovascular Diseases ,Hypertension ,Reactive Oxygen Species ,Oxidative stress - Abstract
An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
- Published
- 2009
13. The molecular sources of reactive oxygen species in hypertension
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Paolo Emilio Puddu, Eleonora Cravero, Marzia Rosati, Giovanni M. Puddu, Antonio Muscari, Puddu P., Puddu G.M., Cravero E., Rosati M., and Muscari A.
- Subjects
Mitochondrial ROS ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Xanthine Dehydrogenase ,Oxidative phosphorylation ,Mitochondrion ,medicine.disease_cause ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Internal medicine ,Internal Medicine ,Medicine ,Animals ,Humans ,Endothelial dysfunction ,Xanthine oxidase ,chemistry.chemical_classification ,Reactive oxygen species ,NADPH oxidase ,biology ,business.industry ,NADPH Oxidases ,General Medicine ,medicine.disease ,Mitochondria ,Oxidative Stress ,Endocrinology ,chemistry ,Hypertension ,biology.protein ,Cardiology and Cardiovascular Medicine ,business ,Reactive Oxygen Species ,Oxidative stress - Abstract
In both animal models and humans, increased blood pressure has been associated with oxidative stress in the vasculature, i.e. an excessive endothelial production of reactive oxygen species (ROS), which may be both a cause and an effect of hypertension. In addition to NADPH oxidase, the best characterized source of ROS, several other enzymes may contribute to ROS generation, including nitric oxide synthase, lipoxygenases, cyclo-oxygenases, xanthine oxidase and cytochrome P450 enzymes. It has been suggested that also mitochondria could be considered a major source of ROS: in situations of metabolic perturbation, increased mitochondrial ROS generation might trigger endothelial dysfunction, possibly contributing to the development of hypertension. However, the use of antioxidants in the clinical setting induced only limited effects on human hypertension or cardiovascular endpoints. More clinical studies are needed to fully elucidate this so called "oxidative paradox" of hypertension.
- Published
- 2008
14. The genetic basis of essential hypertension
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Antonio Muscari, Giovanni M. Puddu, Paolo Emilio Puddu, Eleonora Cravero, Eleonora Ferrari, Puddu P., Puddu G.M., Cravero E., Ferrari E., and Muscari A.
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Aldosterone synthase ,Candidate gene ,Adrenergic receptor ,Nitric Oxide Synthase Type III ,Biology ,Essential hypertension ,DNA, Mitochondrial ,Proinflammatory cytokine ,Renin-Angiotensin System ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Receptor ,Gene ,Genetics ,Polymorphism, Genetic ,Endothelin-1 ,General Medicine ,medicine.disease ,Angiotensin II ,Hypertension ,Mutation ,biology.protein ,Kallikreins ,Receptors, Adrenergic, beta-2 ,Cardiology and Cardiovascular Medicine - Abstract
During the last few years the studies on the genetic basis of essential hypertension (EH) have been numerous, allowing however only a partial understanding of the underlying molecular mechanisms. The most used techniques were the candidate gene approach, genome-wide scanning, the intermediate phenotype approach and comparative-genomics in animal models.The renin-angiotensin-aldosterone system may play a prominent role in the genesis of hypertension, and polymorphisms of the genes coding for angiotensinogen, angiotensin-converting enzyme, angiotensin II type I and 2 receptors, and aldosterone synthase have been widely studied. Other mechanisms may involve the KLK I gene of tissue kallikrein, gene variants of endothelial nitric oxide synthase and polymorphisms of the endothelin- 1 gene. Finally, a number of studies have highlighted the potential contribution of polymorphisms of genes coding for inflammatory cytokines, adrenergic receptors and intracellular G proteins, which can activate Na+/K+ exchangers. Further important information might derive from proteomic analysis and the study of mitochondrial genome. Overall, results have often been discordant, sometimes suggesting a different expression of the same gene variants in different populations. EH is a highly polygenic condition, caused by the combination of small changes in the expression of many genes, in conjunction with a variable collection of environmental factors.
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- 2007
15. Genes and atherosclerosis: at the origin of the predisposition
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P, Puddu, E, Cravero, G M, Puddu, A, Muscari, Puddu P., Cravero E., Puddu G.M., and Muscari A.
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Polymorphism, Genetic ,Genotype ,Arteriosclerosis ,Aryldialkylphosphatase ,Gene Expression ,Lipids ,Models, Biological ,Renin-Angiotensin System ,Risk Factors ,Mutation ,Animals ,Humans ,ATP-Binding Cassette Transporters ,Genetic Predisposition to Disease ,Blood Coagulation ,Methylenetetrahydrofolate Reductase (NADPH2) ,ATP Binding Cassette Transporter 1 - Abstract
Atherosclerosis (ATS) is a multifactorial disease caused by the interaction of established or emerging risk factors with multiple predisposing genes that regulate ATS-related processes. This review will discuss the current knowledge concerning the potential role of the genetic variations that could promote and/or accelerate ATS, in both animal models and humans. Allelic polymorphisms or variations of distinct genes that enhance the risk of ATS frequently occur in the general population, but only adequate gene-environment interactions will lead to the disease. The main genes so far studied are involved in the regulation of processes such as endothelial function, antioxidant potential, coagulation, inflammatory response, and lipid, protein and carbohydrate metabolism. The detection of candidate genes associated with ATS could allow, in the near future, earlier interventions in genetically susceptible individuals. Further, large-scale population studies are needed to obtain more information on the specific gene-environment and drug-gene interactions capable of influencing ATS progression.
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- 2005
16. Molecular aspects of atherogenesis: new insights and unsolved questions
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Eleonora Cravero, Giorgia Arnone, Antonio Muscari, Giovanni M. Puddu, Paolo Emilio Puddu, Puddu G.M., Cravero E., Arnone G., Muscari A., and Puddu P.
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G PROTEINS ,Nitric Oxide Synthase Type III ,G protein ,Endocrinology, Diabetes and Metabolism ,Peroxisome Proliferator-Activated Receptors ,Clinical Biochemistry ,Receptors, Cytoplasmic and Nuclear ,Inflammation ,ATHEROGENESIS ,Biology ,Nitric Oxide ,Receptors, G-Protein-Coupled ,Thromboplastin ,Tissue factor ,LIPOPROTEINS ,Enos ,Cell Adhesion ,medicine ,Animals ,Humans ,Insulin ,Pharmacology (medical) ,Endothelial dysfunction ,Liver X receptor ,Receptor ,Molecular Biology ,Liver X Receptors ,G protein-coupled receptor ,CAVEOLIN ,Biochemistry (medical) ,Arteries ,Cell Biology ,General Medicine ,Atherosclerosis ,Orphan Nuclear Receptors ,medicine.disease ,biology.organism_classification ,Lipids ,Mitochondria ,Cell biology ,DNA-Binding Proteins ,Oxygen ,Biochemistry ,Leukocytes, Mononuclear ,Cytokines ,medicine.symptom ,Reactive Oxygen Species ,OXIDANT STRESS - Abstract
The development of atherosclerotic disease results from the interaction between environment and genetic make up. A key factor in atherogenesis is the oxidative modification of lipids, which is involved in the recruitment of mononuclear leukocytes to the arterial intima – a process regulated by several groups of adhesion molecules and cytokines. Activated leukocytes, as well as endothelial mitochondria, can produce reactive oxygen species (ROS) that are associated with endothelial dysfunction, a cause of reduced nitric oxide (NO) bioactivity and further ROS production. Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are nuclear receptors significantly involved in the control of lipid metabolism, inflammation and insulin sensitivity. Also, an emerging role has been suggested for G protein coupled receptors and for the small Ras and Rho GTPases in the regulation of the expression of endothelial NO synthase (eNOS) and of tissue factor, which are involved in thrombus formation and modulation of vascular tone. Further, the interactions among eNOS, cholesterol, oxidated LDL and caveola membranes are probably involved in some molecular changes observed in vascular diseases. Despite the relevance of oxidative processes in atherogenesis, anti-oxidants have failed to significantly improve atherosclerosis (ATS) prevention, while statins have proved to be the most successful drugs.
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- 2005
17. Different effects of antihypertensive drugs on endothelial dysfunction
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Eleonora Cravero, Antonio Muscari, Giovanni M. Puddu, Paolo Emilio Puddu, Puddu P., Puddu G.M., Cravero E., and Muscari A.
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medicine.medical_specialty ,Angiotensin receptor ,Endothelium ,Arteriosclerosis ,Vasodilation ,Constriction, Pathologic ,Pharmacology ,Essential hypertension ,Internal medicine ,medicine ,Animals ,Humans ,Endothelial dysfunction ,Antihypertensive Agents ,Endothelin-1 ,business.industry ,General Medicine ,medicine.disease ,Angiotensin II ,Nebivolol ,Endocrinology ,medicine.anatomical_structure ,Pathophysiology of hypertension ,Hypertension ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Since endothelial dysfunction may significantly contribute to the pathophysiology of hypertension and its complications, its modification seems to be a very attractive means to favourably affect the development of atherosclerosis and cardiovascular events in hypertensive patients. However, not all antihypertensive drugs consistently improve endothelial dysfunction. While first-generation beta-blockers showed contrasting or null effects on endothelial function, newer beta-blockers of the third generation, such as carvedilol and nebivolol, seem to be provided with specific endothelium-mediated vasodilating effects. Calcium channel blockers are generally able to increase endothelium-dependent vasodilation in several vascular beds, in patients with essential hypertension, probably through multiple mechanisms. Most studies have shown thatACE inhibitors favourably affect endothelial function mainly in the subcutaneous, epicardial and renal circulation, not only by inhibiting the effects of angiotensin II on the endothelium, but also by enhancing bradykinin-induced vasodilation, probably a hyperpolarization-related effect. On the other hand, discordant evidence is available about the effects of angiotensin II receptor type I blockers on endothelial function in patients with essential hypertension, atherosclerosis or diabetes.There are data suggesting that an increased activity of the endothelin- I system may play a role in the blunted endothelium-dependent vasorelaxation of hypertensive patients, an effect that could be contrasted by the use of endothelin-I receptor antagonists. However, to date no substantial clinical efficacy of endothelin-I receptor blockers has been shown in patients with essential hypertension. Finally, other possibly useful compounds in restoring impaired endothelial function in hypertension are some antioxidant agents such as vitamin C, folic acid, the cofactor tetrahydrobiopterin (BH4), L-arginine and the drugs of the statin class.
- Published
- 2004
18. Mitochondrial dysfunction as an initiating event in atherogenesis: a plausible hypothesis
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Giovanni M. Puddu, Paolo Emilio Puddu, Eleonora Cravero, Antonio Muscari, Livia Galletti, Puddu P., Puddu G.M., Cravero E., and Muscari A.
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Mitochondrial DNA ,medicine.medical_specialty ,Programmed cell death ,Endothelium ,Arteriosclerosis ,Mitochondrion ,DNA, Mitochondrial ,Internal medicine ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,Endothelial dysfunction ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Death ,business.industry ,medicine.disease ,Mitochondria ,Lipoproteins, LDL ,Oxidative Stress ,medicine.anatomical_structure ,Mitochondrial respiratory chain ,Endocrinology ,chemistry ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Lipoproteins, HDL ,Reactive Oxygen Species ,Lipoprotein ,DNA Damage - Abstract
It is now widely accepted that oxidant stress and the ensuing endothelial dysfunction play a key role in the pathogenesis of atherosclerosis and cardiovascular diseases. The mitochondrial respiratory chain is the major source of reactive oxygen species as byproducts of normal cell respiration. Mitochondria may also be important targets for reactive oxygen species, which may damage mitochondrial lipids, enzymes and DNA with following mitochondrial dysfunction. Free cholesterol, oxidized low-density lipoprotein and glycated high-density lipoprotein are further possible causes of mitochondrial dysfunction and/or apoptosis. Moreover, in patients with mitochondrial diseases, vascular complications are commonly observed at an early age, often in the absence of traditional risk factors for atherosclerosis. We propose that mitochondrial dysfunction, besides endothelial dysfunction, represents an important early step in the chain of events leading to atherosclerotic disease.
- Published
- 2004
19. Examining the impact of median arcuate ligament-induced celiac artery compression on target vessel patency, long-term survival and device integrity in fenestrated and branched endovascular repairs.
- Author
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Manunga J, Cravero E, Goldman J, Stanberry LI, Stephenson E, Harris KM, and Skeik N
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- Humans, Retrospective Studies, Male, Female, Aged, Aged, 80 and over, Time Factors, Treatment Outcome, Risk Factors, Stents, Aortic Aneurysm, Abdominal surgery, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal mortality, Aortic Aneurysm, Abdominal physiopathology, Median Arcuate Ligament Syndrome physiopathology, Median Arcuate Ligament Syndrome complications, Median Arcuate Ligament Syndrome diagnostic imaging, Computed Tomography Angiography, Endovascular Procedures instrumentation, Endovascular Procedures adverse effects, Vascular Patency, Celiac Artery diagnostic imaging, Celiac Artery physiopathology, Celiac Artery surgery, Blood Vessel Prosthesis Implantation adverse effects, Blood Vessel Prosthesis Implantation instrumentation, Blood Vessel Prosthesis, Prosthesis Design
- Abstract
Objective: To evaluate the impact of celiac artery (CA) compression by median arcuate ligament (MAL) on technical metrics and long-term CA patency in patients with complex aortic aneurysms undergoing fenestrated/branched endograft repairs (F/B-EVARs)., Methods: Single-center, retrospective review of patients undergoing fenestrated/branched endovascular aortic aneurysm repairs and requiring incorporation of the CA between 2013 and 2023. Patients were divided into two groups-those with (MAL+) and without (MAL-) CA compression-based on preoperative computed tomography angiography findings. MAL was classified in three grades (A, B, and C) based on the degree and length of stenosis. Patients with MAL grade A had ≤50% CA stenosis measuring ≤3 mm in length. Those with grade B had 50% to 80% CA stenosis measuring 3 to 8 mm long, whereas those with grade C had >80% stenosis measuring >8 mm in length. End points included device integrity, CA patency and technical success-defined as successful implantation of the fenestrated/branched device with perfusion of CA and no endoleak., Results: One hundred and eighty patients with complex aortic aneurysms (pararenal, 128; thoracoabdominal, 52) required incorporation of the CA during fenestrated/branched endovascular aortic aneurysm repair. Majority (73%) were male, with a median age of 76 years (interquartile range [IQR], 69-81 years) and aneurysm size of 62 mm (IQR, 57-69 mm). Seventy-eight patients (43%) had MAL+ anatomy, including 33 patients with MAL grade A, 32 with grade B, and 13 with grade C compression. The median length of CA stenosis was 7.0 mm (IQR, 5.0-10.0 mm). CA was incorporated using fenestrations in 177 (98%) patients. Increased complexity led to failure in CA bridging stent placement in four MAL+ patients, but completion angiography showed CA perfusion and no endoleak, accounting for a technical success of 100%. MAL+ patients were more likely to require bare metal stenting in addition to covered stents (P = .004). Estimated blood loss, median operating room time, contrast volume, fluoroscopy dose and time were higher (P < .001) in MAL+ group. Thirty-day mortality was 3.3%, higher (5.1%) in MAL+ patients compared with MAL- patients (2.0 %). At a median follow-up of 770 days (IQR, 198-1525 days), endograft integrity was observed in all patients and CA events-kinking (n = 7), thrombosis (n = 1) and endoleak (n = 2) -occurred in 10 patients (5.6%). However, only two patients required reinterventions. MAL+ patients had overall lower long-term survival., Conclusions: CA compression by MAL is a predictor of increased procedural complexity during fenestrated/branched device implantation. However, technical success, long-term device integrity and CA patency are similar to that of patients with MAL- anatomy., Competing Interests: Disclosures J.M. repotrts the use of investigational device in an FDA-approved IDE (G220004) and is a consultant for W. L. Gore & Associates and Medtronic., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
20. Midterm Outcomes of Patients With Complex Aortic Aneurysms Treated Using Mixed and Matched Endoprosthesis From Different Manufacturers.
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Manunga J, Hanif H, Cravero E, Goldman J, Clark RM, Skeik N, Stephenson E, Harris KM, and Rana MA
- Abstract
Objectives: To evaluate outcomes of patients with complex aortic aneurysms (cAAs) undergoing fenestrated/branched endovascular aortic aneurysm repair (f/b-EVAR) using a combination of endoprostheses from different manufacturers., Methods: The study is a 2-center retrospective analysis of prospectively maintained databases of patients with cAAs undergoing f/b-EVAR using a combination of endoprostheses from different manufacturers from 2013 to 2023. Primary endpoints included technical success, major adverse events and reintervention rates. Technical success was defined as implantation of the device without type I or type III endoleak or conversion to open repair. Secondary endpoints included mortality and mid-term device performance., Results: During this time, 353 patients with cAAs underwent f/b-EVARs at both centers. Of these, 80 (22.7%) required use of a combination of devices from 4 different manufacturers for repair. Fifty-one (64%) were treated for thoracoabdominal aortic aneurysms and 29 (36%) for pararenal aneurysms. Majority (74%) were male with a median age of 75 (69, 81) years and aneurysm size of 65 (59, 72) mm. Thirty-five (44%) patients required a proximal thoracic stent graft-W.L. Gore (17), Cook, Medtronic, and Terumo (6), respectively. Seventy-seven (96%) patients required a bifurcated device, including Cook Flex (34), Gore (40), and Medtronic (3). Twelve patients underwent common iliac artery aneurysm repair with a Gore iliac branched endoprosthesis. One hundred fifty-four limbs were implanted: Gore: 68, Cook: 82 and Medtronic: 4. Three hundred fourteen target vessels were incorporated. Median operating room time, estimated blood loss, fluoroscopy time and dose were 209 (186, 278) minutes, 100 (50, 663) mL, 77 (59, 100) minutes, 2385 (1415, 3885) mGy, respectively. Three endoleaks were observed on completion angiography-2 type Ic and 1 type IIIa-all of which resolved at 1 month. Fifteen MAEs were observed in 11 patients at 30 days, including 3 (3.9%) deaths, 7 renal insufficiency, 1 renal failure requiring dialysis, 2 MI and paraplegia, respectively. At a median follow-up of 400 (85, 1132) days, there were 8 reinterventions for endoleaks in 7 patients., Conclusions: The use of mixed devices proximal and distal to f/b-devices built to treat patients with cAAs is safe and has good mid-term results., Clinical Impact: While not yet formally assessed in randomized clinical trials or endorsed by the Food and Drug Administration (FDA), the practice of utilizing devices from various manufacturers to address complex aortic anatomy is widespread in everyday clinical settings, yet outcomes remain insufficiently documented. To our knowledge, ours is the first manuscript demonstrating that the use of endoprostheses from different manufacturers for treating patients with complex aortic aneurysms is both safe and yields favorable mid-term results. This frequently employed strategy warrants further exploration through meticulously designed clinical trials, aiming to furnish vascular specialists with a well-founded guideline based on robust clinical evidence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.M.—Use of investigational device in an FDA-approved IDE (G220004), Consultation for W.L. Gore and Medtronic; H.H.: none; E.C.: none; J.G.: none; R.M.C.: none; E.S.: none, N.S.: none; M.A.R.: consultation for GE imaging.
- Published
- 2024
- Full Text
- View/download PDF
21. Routine Versus Selective Distal Perfusion Catheter Use in Venoarterial Extracorporeal Membrane Oxygenation.
- Author
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Buda KG, Robinson EC, Titus J, Eckman PM, Chavez I, Cravero E, Stanberry L, and Hryniewicz K
- Abstract
Although current studies support the use of prophylactic distal perfusion catheters (DPCs) to decrease limb ischemia in patients on venoarterial extracorporeal membrane oxygenation (VA ECMO), methods for monitoring limb ischemia differ between studies. We evaluated the safety of a selective rather than prophylactic DPC strategy at a single center with a well-established protocol for limb ischemia monitoring. Distal perfusion catheters were placed selectively if there was evidence of hypoperfusion at any point until decannulation. All patients were followed daily by vascular surgery with continuous regional saturation monitoring. Of 188 patients supported with VA ECMO, there were no significant differences in baseline characteristics between patients with upfront, delayed, and no DPC. Thirty day mortality was highest in patients with an upfront DPC (56% in the upfront DPC group, 19% in the delayed DPC group, and 22% in the no-DPC group, p < 0.001). The incidence of major bleeding, fasciotomy, and amputation in the entire cohort was 3.7%, 3.7%, and 0%, respectively. With strict adherence to a protocol for limb ischemia monitoring, a selective rather than prophylactic DPC strategy is safe and may obviate the risks of an additional arterial catheter., Competing Interests: Disclosure: P.M.E .: Consulting for Abbott, Ancora, Daxor, Medtronic. K.H.: Consultant for Abiomed. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)
- Published
- 2024
- Full Text
- View/download PDF
22. Primary and Secondary Tumors of the Parotid Gland: Clinical Features and Prognosis.
- Author
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Pecorari G, Pizzo C, Briguglio M, Cravero E, and Riva G
- Abstract
Primary and secondary malignant tumors can affect the parotid gland. The aim of this retrospective study was to evaluate the clinical features and prognosis of malignant epithelial tumors of the parotid gland. In particular, a comparison between primary and secondary cancer and survival analyses were performed. Eighteen patients with primary cancer and fifteen with intraparotid metastasis from cutaneous squamous cell carcinoma were included. A chart review was performed to collect clinical data (age, sex, smoking, alcohol consumption, tumor stage, type of surgical procedure, complications, recurrence and death). The majority of primary tumors were early (T1-2 N0, 83%) with mucoepidermoid carcinoma being the most common (33%). Secondary tumors were mostly staged P2 (53%) and N0 (67%). Subjects with secondary tumors were older than those with primary cancer. Post-operative permanent facial palsy was observed in 5 patients (17%) with primary cancer and 9 (60%) with secondary tumors ( p = 0.010). Two-year overall survival for primary and secondary parotid cancer was 76.58% and 43.51%, respectively ( p = 0.048), while 2-year disease-free survival was 76.05% and 38.50%, respectively ( p = 0.152). In conclusion, secondary cancer of the parotid gland has worse survival than primary tumors. In the future, the implementation of multimodality treatment of intraparotid metastases is necessary to improve oncologic outcomes.
- Published
- 2023
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- View/download PDF
23. The Flex Robotic System in Head and Neck Surgery: A Review.
- Author
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Riva G, Cravero E, Briguglio M, Capaccio P, and Pecorari G
- Abstract
The Flex Robotic System is a device intended for robot-assisted visualization and surgical site access to the head and neck. The aim of this review is to summarize the current knowledge about the Flex Robotic System in head and neck transoral robotic surgery (TORS). The primary search was performed using the term "Flex Robot" across several databases (PubMed, Embase, Cochrane, Scopus). Patients were treated for both benign and malignant diseases. The oropharynx was the most frequent site of disease, followed by the supraglottic larynx, hypopharynx, glottic larynx, oral cavity, and salivary glands. Most of the studies did not reveal major intra- or post-operative complications. Bleeding incidence was low (1.4-15.7%). Visualization of the lesion was 95-100%, while surgical success was 91-100%. In conclusion, lesions of the oropharynx, hypopharynx, or larynx can be successfully resected, thus making the Flex Robotic System a safe and effective tool, reducing the morbidity associated with traditional open surgery.
- Published
- 2022
- Full Text
- View/download PDF
24. Post-Operative Infections in Head and Neck Cancer Surgery: Risk Factors for Different Infection Sites.
- Author
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Pecorari G, Riva G, Albera A, Cravero E, Fassone E, Canale A, and Albera R
- Abstract
Background: Post-operative infections in head and neck cancer (HNC) surgery represent a major problem and are associated with an important increase in mortality, morbidity, and burden on the healthcare system. The aim of this retrospective observational study was to evaluate post-operative infections in HNC surgery and to analyze risk factors, with a specific focus on different sites of infection., Methods: Clinical data about 488 HNC patients who underwent surgery were recorded. Univariate and multivariate analyses were performed to identify risk factors for post-operative infections., Results: Post-operative infections were observed in 22.7% of cases. Respiratory and surgical site infections were the most common. Multiple site infections were observed in 3.9% of cases. Considering all infection sites, advanced stage, tracheotomy, and higher duration of surgery were risk factors at multivariate analysis. Median hospital stay was significantly longer in patients who had post-operative infection (38 vs. 9 days)., Conclusions: Post-operative infections may negatively affect surgical outcomes. A correct identification of risk factors may help the physicians to prevent post-operative infections in HNC surgery.
- Published
- 2022
- Full Text
- View/download PDF
25. Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review.
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Riva G, Cravero E, Pizzo C, Briguglio M, Iorio GC, Cavallin C, Ostellino O, Airoldi M, Ricardi U, and Pecorari G
- Abstract
Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life.
- Published
- 2022
- Full Text
- View/download PDF
26. Unilateral Poststroke Periodic Limb Movements: A Case Series.
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Coletti Moja M, Cravero E, Logozzo I, Mairano C, and Labate C
- Abstract
Periodic limb movements (PLM) and restless leg syndrome (RLS) are involuntary common sleep-related movements which often hamper sleep onset; they are mostly idiopathic and bilateral but are seldom described secondary after a stroke. These cases are rare, often unilateral, and because of the usually transitory duration of symptoms, often under-recognized. When a treatment is required, it can be tricky and the drug choice not foregone. We report 2 patients with unilateral poststroke PLM with similar clinical pictures but different symptoms, therapy, and outcome. The first is a long-lasting unilateral PLM video case with chronic vascular lesions leading to insomnia even if with no urgence or any subjective symptoms as in RLS but well responding only to a definite RLS treatment. The second case is an acute, short-duration self-limiting PLM with positive brain MRI lesion imaging. Our cases suggest that unilateral poststroke PLM even if distinct in subjective and radiological features from secondary RLS can sometimes have a definite and effective dopaminergic treatment if long-lasting. Putative mechanism of chronic case 1 PLM could be due to a further stroke sparing sensory pathways and making the patient unaware of subjective RLS-like symptoms., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)
- Published
- 2022
- Full Text
- View/download PDF
27. Long-term evaluation of nasal polyposis recurrence: A focus on multiple relapses and nasal cytology.
- Author
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Riva G, Tavassoli M, Cravero E, Moresco M, Albera A, Canale A, and Pecorari G
- Subjects
- Chronic Disease, Humans, Recurrence, Retrospective Studies, Nasal Polyps surgery, Rhinitis surgery, Sinusitis surgery
- Abstract
Purpose: Recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) is highly variable, reaching 55-60% of cases. Different results about clinical parameters as recurrence predictors has been reported. The aim of this retrospective study was to evaluate CRSwNP recurrence risk after a long-term follow-up (up to 20 years). Moreover, the role of nasal cytology was assessed., Materials and Methods: Sixty-one patients who underwent functional endoscopic sinus surgery for CRSwNP were enrolled. Clinical parameters were recorded. Nasal cytology was performed at follow-up examinations. The Kaplan-Meier method was used to obtain the recurrence-free survival curves. The median number of recurrences per year was evaluated., Results: Five- and 10-year recurrence rates were 30.29% and 66.06%, respectively. Median recurrence-free survival was 106 months. Asthma and Aspirin-Exacerbated Respiratory Disease represented predictors of multiple recurrences (p < 0.05). Intranasal steroids were the main treatment to prevent relapses (p < 0.05). Patients with normal cytology at follow-up evaluation had a lower probability to have first recurrence within 10 years (59% of cases), compared to neutrophil or eosinophil infiltrate (100% and 88% of cases, respectively) (p < 0.05)., Conclusions: CRSwNP has a high recurrence risk, also more than 10 years after surgery. Nasal cytology may identify subjects with a higher risk of early recurrence., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. Histological evaluation of acetabular bone quality during revision hip arthroplasty.
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Bistolfi A, Linari A, Aprato A, Fusini F, Cravero E, Papotti M, Ferracini R, and Massè A
- Subjects
- Acetabulum diagnostic imaging, Acetabulum surgery, Aged, Follow-Up Studies, Humans, Middle Aged, Prosthesis Failure, Reoperation, Retrospective Studies, Arthroplasty, Replacement, Hip adverse effects, Hip Prosthesis
- Abstract
Purpose: Aim of this study was to evaluate acetabular bone vitality during revision hip arthroplasty and to compare the bone quality between revision and primary acetabular arthroplasty., Methods: During primary and revision total hip arthroplasty surgeries, biopsies were taken from the acetabulum after reaming. The samples (osteochondral cylinders of approximately ⩽1 cm long and 3 mm thickness), after removing the mineral component, were cut longitudinally with a thickness section of 5 µm and colored with hematoxylin-eosin dichromic dye and then evaluated histologically by optical microscopy with 40× magnification. Preoperative radiographs were evaluated., Results: According to inclusion and exclusion criteria, 14 patients formed the revision group patients (mean age: 67.9 years, average time before revision 8.8 years, SD ± 7.06) and 5 patients formed the control primary group (mean age: 61.4 years). The bone quality of the revision group was generally poorer than the primary group, while similar vitality and bone quality has been found between septic and aseptic group. Variables such as age, gender and BMI did not significantly contribute to define bone quality classes., Conclusions: The study confirms the differences in quality and bone vitality between cases and controls and the necessity to find strategies to improve the osteointegrative processes in revision arthroplasties.
- Published
- 2020
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29. Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications.
- Author
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Puddu P, Puddu GM, Cravero E, Vizioli L, and Muscari A
- Subjects
- Allopurinol pharmacology, Allopurinol therapeutic use, Antioxidants, Atherosclerosis drug therapy, Atherosclerosis etiology, Atherosclerosis prevention & control, Cardiovascular Diseases drug therapy, Humans, Molecular Targeted Therapy, Oxidative Stress, Oxypurinol pharmacology, Oxypurinol therapeutic use, Reactive Oxygen Species metabolism, Risk Factors, Uric Acid metabolism, Cardiovascular Diseases etiology, Endothelium, Vascular physiopathology, Hyperuricemia complications, Uric Acid adverse effects, Xanthine Dehydrogenase antagonists & inhibitors, Xanthine Dehydrogenase physiology
- Abstract
Uric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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- View/download PDF
30. The functional role of dendritic cells in atherogenesis (Review).
- Author
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Puddu P, Puddu GM, Cravero E, Muscari S, and Muscari A
- Abstract
Accumulating evidence suggests that dendritic cells (DCs) play a crucial role in the generation and progression of atherosclerosis (ATS), a lipid-related immuno-inflammatory disease. DCs have the ability to process and present antigens (mainly oxidized low-density lipoproteins, heat shock proteins and fragments of necrotic or apoptotic cells) to naive T cells, and the activation of T cells is a key step for the progression of atherosclerotic disease. The existence of some distinct DC subtypes has now become evident. The main categories of DC subsets are the 'conventional or myeloid' and the 'plasmacytoid', which differ in toll-like receptor type and site of expression, pathogens and antigens recognized, and effector cytokines and functions. Studies on the potential impact of DCs in the pathogenesis of ATS may lead to novel therapies to regulate the immunoreactions occurring in atherogenesis. In particular, diltiazem, peroxisome proliferator activated receptor agonists and statins have been shown to protect endothelial cell function by inhibiting DCs, a mechanism that may play a significant role in the prevention of ATS.
- Published
- 2010
- Full Text
- View/download PDF
31. The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases.
- Author
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Puddu P, Puddu GM, Cravero E, Muscari S, and Muscari A
- Subjects
- Cardiovascular Diseases blood, Cell Membrane physiology, Endothelium, Vascular physiology, Humans, Platelet Aggregation physiology, Platelet Aggregation Inhibitors therapeutic use, Blood Coagulation physiology, Blood Platelets physiology, Cell-Derived Microparticles physiology, Inflammation blood
- Abstract
Microparticles (MPs) are small vesicles, ranging in size from 0.1 microm to 2 microm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.
- Published
- 2010
- Full Text
- View/download PDF
32. The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis.
- Author
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Puddu P, Puddu GM, Cravero E, De Pascalis S, and Muscari A
- Subjects
- Animals, Antioxidants chemistry, Atherosclerosis physiopathology, DNA, Mitochondrial metabolism, Diabetes Mellitus pathology, Dyslipidemias pathology, Endothelial Cells pathology, Humans, Hypertension pathology, Macrophages pathology, Mitochondria metabolism, Oxidative Stress, Reactive Oxygen Species, Risk Factors, Atherosclerosis metabolism, Cardiovascular Diseases pathology, Mitochondria pathology
- Abstract
An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
- Published
- 2009
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- View/download PDF
33. The complexity of platelet metabolism and its contribution to atherothrombosis.
- Author
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Puddu P, Muscari A, Puddu GM, Cravero E, Giannoni C, and Zoli M
- Subjects
- Animals, Atherosclerosis blood, Humans, Platelet Aggregation physiology, Prognosis, Risk Factors, Thrombosis etiology, Atherosclerosis complications, Blood Platelets metabolism, Thrombosis blood
- Abstract
Platelet functions are multiple, complex and not limited to haemostasis. In fact, platelets play a relevant role in vascular inflammation and atherosclerosis (ATS). In the presence of vascular lesions or inflammation, endothelial denudation or activation triggers mechanisms that render the circulating platelets adhesive for the vascular wall. Endothelial lesions expose subendothelial matrix components, such as collagen, von Willebrand factor, fibronectin and other adhesive proteins. Platelet adhesion depends on the interaction between these components and platelet receptors (mainly glycoprotein (GP) VI and GPlb-IX-V). Adhesion triggers the platelet release of inflammatory and mitogenic substances that alter the thromboresistant endothelial surface, enhance the chemoattraction of leukocytes, stimulate smooth muscle cell proliferation and contribute to matrix degradation. Finally, GPIIb-IIIa receptors are activated, leading to firm platelet aggregation and thrombus formation. Platelets participate in the formation of mural thrombi in the late stages of atherosclerotic disease, but also adhere to endothelial cells during the earlier stages of atherosclerotic plaque development. Moreover, platelets exert important functions in modulating inflammatory and immune processes. An improved comprehension of the complex platelet pathophysiology could suggest new therapeutic strategies to reduce the impact of atherosclerotic disease.
- Published
- 2009
- Full Text
- View/download PDF
34. The molecular sources of reactive oxygen species in hypertension.
- Author
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Puddu P, Puddu GM, Cravero E, Rosati M, and Muscari A
- Subjects
- Animals, Cytochrome P-450 Enzyme System physiology, Humans, Mitochondria metabolism, NADPH Oxidases physiology, Nitric Oxide Synthase Type III physiology, Oxidative Stress, Xanthine Dehydrogenase physiology, Hypertension metabolism, Reactive Oxygen Species metabolism
- Abstract
In both animal models and humans, increased blood pressure has been associated with oxidative stress in the vasculature, i.e. an excessive endothelial production of reactive oxygen species (ROS), which may be both a cause and an effect of hypertension. In addition to NADPH oxidase, the best characterized source of ROS, several other enzymes may contribute to ROS generation, including nitric oxide synthase, lipoxygenases, cyclo-oxygenases, xanthine oxidase and cytochrome P450 enzymes. It has been suggested that also mitochondria could be considered a major source of ROS: in situations of metabolic perturbation, increased mitochondrial ROS generation might trigger endothelial dysfunction, possibly contributing to the development of hypertension. However, the use of antioxidants in the clinical setting induced only limited effects on human hypertension or cardiovascular endpoints. More clinical studies are needed to fully elucidate this so called "oxidative paradox" of hypertension.
- Published
- 2008
- Full Text
- View/download PDF
35. The putative role of mitochondrial dysfunction in hypertension.
- Author
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Puddu P, Puddu GM, Cravero E, De Pascalis S, and Muscari A
- Subjects
- Animals, DNA, Mitochondrial, Electron Transport, Endothelium, Vascular physiopathology, Humans, Hypertension physiopathology, Ion Channels metabolism, Mitochondrial Proteins metabolism, Uncoupling Protein 1, Hypertension metabolism, Mitochondria metabolism, Oxidative Stress, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism
- Abstract
Hypertension is a condition associated with oxidative stress, endothelial dysfunction, and increased vascular resistance, representing probably both a cause and a consequence of elevated levels of reactive oxygen (ROS) and nitrogen (RNS) species. Mitochondria are important sites of ROS production, and a mitochondrial dysfunction, preceding endothelial dysfunction, might favor the development of hypertension. ROS production may also be induced by RNS, which inhibit the respiratory chain and may be generated through the action of a mitochondrial NO synthase. Mitochondrial uncoupling proteins are involved in both experimental and human hypertension. Finally, an excessive production of ROS may damage mitochondrial DNA, with resultant impairment in the synthesis of some components of the respiratory chain and further ROS production, a vicious cycle that may be implicated in hypertensive states.
- Published
- 2007
- Full Text
- View/download PDF
36. Gene-based therapy for hypertension--do preclinical data suggest a promising future?
- Author
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Puddu GM, Cravero E, Ferrari E, Muscari A, and Puddu P
- Subjects
- Animals, Disease Models, Animal, Female, Forecasting, Gene Transfer Techniques, Genetic Vectors, Humans, Hypertension genetics, Male, Mice, Oligonucleotides, Antisense genetics, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Rats, Rats, Inbred SHR, Renin-Angiotensin System genetics, Risk Factors, Sensitivity and Specificity, Genetic Therapy methods, Hypertension therapy, Oligonucleotides, Antisense pharmacology
- Abstract
Many experimental studies have obtained a prolonged control of blood pressure through gene treatment. This consists in the administration of genes coding for vasodilator proteins (the 'sense' approach), or of nucleotide sequences that are complementary to the mRNA of vasoconstrictor proteins, which are consequently synthesized in smaller amounts (the 'antisense' approach). Examples of the sense approach include the genes encoding endothelial nitric oxide synthase and kallikrein. Examples of the second type of approach are the antisense oligodeoxynucleotides to angiotensin-converting enzyme and endothelin-1. Also, RNA molecules, such as ribozymes and small interfering RNAs, are capable to inhibit RNA function. Whole sense genes are usually administered through viral vectors, while antisense oligonucleotides may be administered with plasmids or liposomes. Both viral and non-viral vectors have advantages and disadvantages. Despite the still persisting limitations, the possibility exists that in the future some forms of genetic treatment will be extended to the clinical setting, allowing a prolonged control of essential hypertension and its end-organ sequelae., (Copyright 2007 S. Karger AG, Basel.)
- Published
- 2007
- Full Text
- View/download PDF
37. Molecular aspects of atherogenesis: new insights and unsolved questions.
- Author
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Puddu GM, Cravero E, Arnone G, Muscari A, and Puddu P
- Subjects
- Animals, Arteries metabolism, Cell Adhesion, Cytokines metabolism, DNA-Binding Proteins metabolism, Humans, Inflammation, Insulin metabolism, Leukocytes, Mononuclear metabolism, Lipids chemistry, Liver X Receptors, Mitochondria metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Orphan Nuclear Receptors, Oxygen metabolism, Peroxisome Proliferator-Activated Receptors metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Receptors, G-Protein-Coupled metabolism, Thromboplastin metabolism, Atherosclerosis pathology, Reactive Oxygen Species
- Abstract
The development of atherosclerotic disease results from the interaction between environment and genetic make up. A key factor in atherogenesis is the oxidative modification of lipids, which is involved in the recruitment of mononuclear leukocytes to the arterial intima--a process regulated by several groups of adhesion molecules and cytokines. Activated leukocytes, as well as endothelial mitochondria, can produce reactive oxygen species (ROS) that are associated with endothelial dysfunction, a cause of reduced nitric oxide (NO) bioactivity and further ROS production. Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are nuclear receptors significantly involved in the control of lipid metabolism, inflammation and insulin sensitivity. Also, an emerging role has been suggested for G protein coupled receptors and for the small Ras and Rho GTPases in the regulation of the expression of endothelial NO synthase (eNOS) and of tissue factor, which are involved in thrombus formation and modulation of vascular tone. Further, the interactions among eNOS, cholesterol, oxidated LDL and caveola membranes are probably involved in some molecular changes observed in vascular diseases. Despite the relevance of oxidative processes in atherogenesis, anti-oxidants have failed to significantly improve atherosclerosis (ATS) prevention, while statins have proved to be the most successful drugs.
- Published
- 2005
- Full Text
- View/download PDF
38. Mitochondrial dysfunction as an initiating event in atherogenesis: a plausible hypothesis.
- Author
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Puddu P, Puddu GM, Galletti L, Cravero E, and Muscari A
- Subjects
- Animals, Cell Death, DNA Damage physiology, Humans, Lipoproteins, HDL physiology, Lipoproteins, LDL physiology, Mitochondria metabolism, Reactive Oxygen Species metabolism, Arteriosclerosis physiopathology, DNA, Mitochondrial metabolism, Endothelium, Vascular metabolism, Mitochondria physiology, Oxidative Stress physiology
- Abstract
It is now widely accepted that oxidant stress and the ensuing endothelial dysfunction play a key role in the pathogenesis of atherosclerosis and cardiovascular diseases. The mitochondrial respiratory chain is the major source of reactive oxygen species as byproducts of normal cell respiration. Mitochondria may also be important targets for reactive oxygen species, which may damage mitochondrial lipids, enzymes and DNA with following mitochondrial dysfunction. Free cholesterol, oxidized low-density lipoprotein and glycated high-density lipoprotein are further possible causes of mitochondrial dysfunction and/or apoptosis. Moreover, in patients with mitochondrial diseases, vascular complications are commonly observed at an early age, often in the absence of traditional risk factors for atherosclerosis. We propose that mitochondrial dysfunction, besides endothelial dysfunction, represents an important early step in the chain of events leading to atherosclerotic disease., (Copyright 2005 S. Karger AG, Basel.)
- Published
- 2005
- Full Text
- View/download PDF
39. Different effects of antihypertensive drugs on endothelial dysfunction.
- Author
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Puddu P, Puddu GM, Cravero E, and Muscari A
- Subjects
- Animals, Antihypertensive Agents classification, Antihypertensive Agents therapeutic use, Arteriosclerosis physiopathology, Arteriosclerosis prevention & control, Constriction, Pathologic drug therapy, Endothelin-1 antagonists & inhibitors, Humans, Hypertension physiopathology, Hypertension prevention & control, Vasodilation drug effects, Antihypertensive Agents pharmacology, Endothelium, Vascular drug effects, Endothelium, Vascular physiopathology
- Abstract
Since endothelial dysfunction may significantly contribute to the pathophysiology of hypertension and its complications, its modification seems to be a very attractive means to favourably affect the development of atherosclerosis and cardiovascular events in hypertensive patients. However, not all antihypertensive drugs consistently improve endothelial dysfunction. While first-generation beta-blockers showed contrasting or null effects on endothelial function, newer beta-blockers of the third generation, such as carvedilol and nebivolol, seem to be provided with specific endothelium-mediated vasodilating effects. Calcium channel blockers are generally able to increase endothelium-dependent vasodilation in several vascular beds, in patients with essential hypertension, probably through multiple mechanisms. Most studies have shown thatACE inhibitors favourably affect endothelial function mainly in the subcutaneous, epicardial and renal circulation, not only by inhibiting the effects of angiotensin II on the endothelium, but also by enhancing bradykinin-induced vasodilation, probably a hyperpolarization-related effect. On the other hand, discordant evidence is available about the effects of angiotensin II receptor type I blockers on endothelial function in patients with essential hypertension, atherosclerosis or diabetes.There are data suggesting that an increased activity of the endothelin- I system may play a role in the blunted endothelium-dependent vasorelaxation of hypertensive patients, an effect that could be contrasted by the use of endothelin-I receptor antagonists. However, to date no substantial clinical efficacy of endothelin-I receptor blockers has been shown in patients with essential hypertension. Finally, other possibly useful compounds in restoring impaired endothelial function in hypertension are some antioxidant agents such as vitamin C, folic acid, the cofactor tetrahydrobiopterin (BH4), L-arginine and the drugs of the statin class.
- Published
- 2004
- Full Text
- View/download PDF
40. [COX-2 inhibitors: a new treatment in rheumatic diseases].
- Author
-
Puddu G and Cravero E
- Subjects
- Aged, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Celecoxib, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors administration & dosage, Cyclooxygenase Inhibitors adverse effects, Humans, Membrane Proteins, Prostaglandin-Endoperoxide Synthases, Pyrazoles, Risk Factors, Sulfonamides administration & dosage, Sulfonamides adverse effects, Time Factors, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Arthritis, Rheumatoid drug therapy, Cyclooxygenase Inhibitors therapeutic use, Isoenzymes antagonists & inhibitors, Osteoarthritis drug therapy, Sulfonamides therapeutic use
- Abstract
Progressive increase of the average lifespan pushed up the number of the elderlies in the population. The subsequent spread of degenerative conditions such as osteoarthritis has inflated the request of NSAID despite their frequent toxicity. Side effects of NSAID are sometimes severe and mainly target gastrointestinal tract, renal and platelets function. It has been estimated that around 70% of the patients treated with NSAID develop some degree of gastric damage, ranging from aspecific dyspeptic syndromes to ulcerative diseases. Drugs are now available that selectively inhibit the cyclooxygenase-2: this enzyme is involved in the synthesis of prostaglandins during the inflammatory response. These new drugs have opened new perspectives in the treatment of arthritis; they allow COX-1 to work regularly, so that those prostaglandins that are involved in the maintenance of a regular function of the gastrointestinal tract mucosa and of the platelets. Celecoxib was the firstborn of these new drugs. Differently from FANS, COXIB has got less side effects on gastrointestinal tract and platelets function. Based on the evidence of the more recent clinical experience COXIB has to be recommended; in particular celecoxib, at a schedule of 200-400 mg/die, was shown to be highly effective in the symptomatic treatment of osteoarthritis and rheumatoid arthritis.
- Published
- 2003
41. [Beta blockers and cardiac decompensation].
- Author
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Puddu GM, Cravero E, and Puddu P
- Subjects
- Humans, Adrenergic beta-Antagonists therapeutic use, Heart Failure drug therapy
- Abstract
It has been demonstrated that beta blockers are able to modify the course of the disease, through the reduction of hemodynamic in stabilization and mortality cases. The success of these drugs in the treatment of chronic heart failure is related to the sympathoadrenergic activation and to renin-angiothensin-aldosteron system. Various molecules are available at the moment. Recent research has been done on third generation beta blockers (carvedilol, nebivolol, bucindolol). These drugs have shown to possess some peculiar characteristics, in particular the ability of reducing the number of side effects which may be seen while using beta blockers of the first generations. Although it is currently difficult to give general informations based only on the pharmacologic profile, the choice of the type of drug to use in the single patient with chronic heart failure should be made considering the adequacy of the pharmacologic characteristics in each specific situation.
- Published
- 1999
42. [Surgery of the abdominal aorta and iliac artery. Risk factors and results].
- Author
-
De Simone F, Pauletti GC, Enrico G, Cravero E, Girivetto F, and Aschieri F
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Risk, Aneurysm surgery, Aorta, Abdominal, Aortic Aneurysm surgery, Arterial Occlusive Diseases surgery, Iliac Artery
- Published
- 1987
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