16 results on '"Candido, Riccardo"'
Search Results
2. Type 1 diabetes is associated with significant changes of ACE and ACE2 expression in peripheral blood mononuclear cells.
- Author
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Tonon, Federica, Candido, Riccardo, Toffoli, Barbara, Tommasi, Elisabetta, Cortello, Thomas, Fabris, Bruno, and Bernardi, Stella
- Abstract
Background and Aims: The renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the "alternative" one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D).Methods and Results: This is a case-control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women.Conclusion: T1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
3. Personalized therapy algorithms for type 2 diabetes: a phenotype-based approach.
- Author
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Ceriello, Antonio, Gallo, Marco, Candido, Riccardo, De Micheli, Alberto, Esposito, Katherine, Gentile, Sandro, and Medea, Gerardo
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ALGORITHMS ,DIABETES ,DISEASE progression ,HYPERGLYCEMIA ,BODY mass index - Abstract
Type 2 diabetes is a progressive disease with a complex and multifactorial pathophysiology. Patients with type 2 diabetes show a variety of clinical features, including different "phenotypes" of hyperglycemia (eg, fasting/preprandial or postprandial). Thus, the best treatment choice is sometimes difficult to make, and treatment initiation or optimization is postponed. This situation may explain why, despite the existing complex therapeutic armamentarium and guidelines for the treatment of type 2 diabetes, a significant proportion of patients do not have good metabolic control and at risk of developing the late complications of diabetes. The Italian Association of Medical Diabetologists has developed an innovative personalized algorithm for the treatment of type 2 diabetes, which is available online. According to the main features shown by the patient, six algorithms are proposed, according to glycated hemoglobin (HbA
1c , ⩾9% or ⩽9%), body mass index (⩽30 kg/m2 or ⩾30 kg/m2 ), occupational risk potentially related to hypoglycemia, chronic renal failure, and frail elderly status. Through self-monitoring of blood glucose, patients are phenotyped according to the occurrence of fasting/preprandial or postprandial hyperglycemia. In each of these six algorithms, the gradual choice of treatment is related to the identified phenotype. With one exception, these algorithms contain a stepwise approach for patients with type 2 diabetes who are metformin-intolerant. The glycemic targets (HbA1c, fasting/preprandial and postprandial glycemia) are also personalized. This accessible and easy to use algorithm may help physicians to choose a personalized treatment plan for each patient and to optimize it in a timely manner, thereby lessening clinical inertia. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
4. Linking diabetes and atherosclerosis.
- Author
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Candido, Riccardo, Bernardi, Stella, and Allen, Terri J.
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TREATMENT of diabetes ,ATHEROSCLEROSIS ,CARDIOVASCULAR disease related mortality ,HYPERGLYCEMIA ,RECEPTOR for advanced glycation end products (RAGE) ,DYSLIPIDEMIA ,INFLAMMATION - Abstract
Cardiovascular diseases are the major causes of morbidity and mortality in people with diabetes. Macroangiopathy in diabetes is manifested by more accelerated and progressive atherosclerosis, which is more widely distributed. The pathogenesis of this accelerated atherosclerosis is multifactorial and includes very complex interactions. Several abnormalities - such as hyperglycemia, dyslipidemia, hypertension, endothelial dysfunction, renin-angiotensin system activation and chronic subclinical inflammation - all appear to play important roles in the development of diabetes-induced atherosclerosis. Treatment of the residual risk, other than glycemia, blood pressure and low-density lipoprotein cholesterol, remains important as the rate of diabetes increases worldwide. A synergistic multifactorial approach against both conventional cardiovascular risk factors and emerging risk factors, such as vasoactive systems, the AGE-RAGE axis, novel proteins, such as TRAIL, and the complement system, as well as oxidative stress and inflammation, may be a promising way to prevent macrovascular disease in diabetes. In this review we focus on the major causes and mechanisms of atherosclerotic disease in patients with diabetes and highlight emerging targets for therapeutic intervention. INSETS: Box 1. TNF-related apoptosis-inducing ligand function in …;Box 2. Effects of osteoprotegerin in the vascular system.;Key issues. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
5. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis.
- Author
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Forbes, Josephine M., Yee, Louis Teo Loon, Thallas, Vicki, Lassila, Markus, Candido, Riccardo, Jandeleit-Dahm, Karin A., Thomas, Merlin C., Burns, Wendy C., Deemer, Elizabeth K., Thorpe, Susan M., Cooper, Mark E., Allen, Terri J., and Thorpe, Susan R
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DIABETES ,ATHEROSCLEROSIS ,STREPTOZOTOCIN ,APOLIPOPROTEIN E ,LABORATORY mice ,ATHEROSCLEROTIC plaque ,PEOPLE with diabetes - Abstract
Advanced glycation end product (AGE) formation may contribute to the progression of atherosclerosis, particularly in diabetes. The present study explored atherosclerosis in streptozotocin-induced diabetic apolipoprotein E-deficient (apoE-/-) mice that were randomized (n = 20) to receive for 20 weeks no treatment, the AGE cross-link breaker ALT-711, or the inhibitor of AGE formation aminoguanidine (AG). A sixfold increase in plaque area with diabetes was attenuated by 30% with ALT-711 and by 40% in AG-treated mice. Regional distribution of plaque demonstrated no reduction in plaque area or complexity within the aortic arch with treatment, in contrast to the thoracic and abdominal aortas, where significant attenuation was seen. Diabetes-associated accumulation of AGEs in aortas and plasma and decreases in skin collagen solubility were ameliorated by both treatments, in addition to reductions in the vascular receptor for AGE. Collagen-associated reductions in the AGEs carboxymethyllysine and carboxyethyllysine were identified with both treatments. Diabetes was also accompanied by aortic accumulation of total collagen, specifically collagens I, III, and IV, as well as increases in the profibrotic cytokines transforming growth factor-beta and connective tissue growth factor and in cellular alpha-smooth muscle actin. Attenuation of these changes was seen in both treated diabetic groups. ALT-711 and AG demonstrated the ability to reduce vascular AGE accumulation in addition to attenuating atherosclerosis in these diabetic mice. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
6. Improved islet morphology after blockade of the renin- angiotensin system in the ZDF rat.
- Author
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Tikellis, Christos, Wookey, Peter J., Candido, Riccardo, Andrikopoulos, Sof, Thomas, Merlin C., and Cooper, Mark E.
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DIABETES ,ANGIOTENSINS ,ENDOCRINE diseases ,PANCREAS ,APOPTOSIS ,PEOPLE with diabetes - Abstract
The renin-angiotensin system (RAS) has an important role in the endocrine pancreas. Although angiotensin II has significant effects on cell proliferation and apoptosis, the contribution of the RAS to changes in islet structure and function associated with type 2 diabetes is yet to be defined. This study examined the specific effects of RAS blockade on islet structure and function in diabetes. Thirty-six male Zucker diabetic fatty (ZDF) rats, 10 weeks of age, were randomized to receive the angiotensin-converting enzyme inhibitor perindopril (8 mg/l in drinking water; n = 12), irbesartan (15 mg/kg via gavage; n = 12), or no treatment (n = 12) for 10 weeks. Results were compared with lean littermates (ZL) (n = 12) studied concurrently. ZDF rats had increased intraislet expression of components of the RAS correlating with increased intraislet fibrosis, apoptosis, and oxidative stress. Disordered islet architecture, seen in ZDF rats, was attenuated after treatment with perindopril or irbesartan. Islet fibrogenesis was also diminished, as measured by picrosirins staining and expression of collagens I and IV. Gene expression of transforming growth factor-β1 was increased in the ZDF pancreas (ZL, 1.0 ± 0.1; ZDF, 2.0 ± 0.3; P < 0.05) and reduced after blockade of the RAS (ZDF + P, 1.3 ± 0.2; ZDF + I, 1.5 ± 0.1; vs. ZDF, both P < 0.05). Improvements in structural parameters were also associated with functional improvements in first-phase insulin secretion. These findings provide a possible mechanism for the reduced incidence of new-onset diabetes that has been observed in clinical trials of RAS blockade. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
7. Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets
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Toffoli, Barbara, Bernardi, Stella, Candido, Riccardo, Sabato, Nicoletta, Carretta, Renzo, Corallini, Federica, Secchiero, Paola, Zauli, Giorgio, and Fabris, Bruno
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TUMOR necrosis factor receptors , *LABORATORY mice , *ISLANDS of Langerhans , *PANCREATIC beta cells , *DRUG administration , *RENIN-angiotensin system , *APOPTOSIS , *GROWTH factors - Abstract
Abstract: Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin–angiotensin system (RAS). OPG-treated mice showed increased islet monocyte/macrophage infiltration, fibrosis and apoptosis with reduction of islet function. The remodeling of islet architecture was associated with increased pancreatic expression of components of the RAS, growth factor genes (transforming growth factor β and connective tissue growth factor) and inflammatory molecules (monocyte chemotactic protein-1 and vascular adhesion molecule type 1). Prevention of these changes with improvement of insulin secretion was observed in ramipril treated animals. Our data suggest that OPG might play an important role in promoting beta cell dysfunction and that the upregulation of the local RAS represents one possible mechanism responsible for the OPG-induced beta cell dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
8. Deep-learning-based prognostic modeling for incident heart failure in patients with diabetes using electronic health records: A retrospective cohort study
- Author
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Ilaria Gandin, Sebastiano Saccani, Andrea Coser, Arjuna Scagnetto, Chiara Cappelletto, Riccardo Candido, Giulia Barbati, Andrea Di Lenarda, Gandin, Ilaria, Saccani, Sebastiano, Coser, Andrea, Scagnetto, Arjuna, Cappelletto, Chiara, Candido, Riccardo, Barbati, Giulia, and Di Lenarda, Andrea
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Multidisciplinary ,Diabetes ,Electronic Health Records ,Heart failure ,Deep learning ,Prognostic model ,Electronic Health Record ,Diabete - Abstract
Patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing heart failure (HF) compared to patients without diabetes. The present study is aimed to build an artificial intelligence (AI) prognostic model that takes in account a large and heterogeneous set of clinical factors and investigates the risk of developing HF in diabetic patients. We carried out an electronic health records- (EHR-) based retrospective cohort study that included patients with cardiological clinical evaluation and no previous diagnosis of HF. Information consists of features extracted from clinical and administrative data obtained as part of routine medical care. The primary endpoint was diagnosis of HF (during out-of-hospital clinical examination or hospitalization). We developed two prognostic models using (1) elastic net regularization for Cox proportional hazard model (COX) and (2) a deep neural network survival method (PHNN), in which a neural network was used to represent a non-linear hazard function and explainability strategies are applied to estimate the influence of predictors on the risk function. Over a median follow-up of 65 months, 17.3% of the 10,614 patients developed HF. The PHNN model outperformed COX both in terms of discrimination (c-index 0.768 vs 0.734) and calibration (2-year integrated calibration index 0.008 vs 0.018). The AI approach led to the identification of 20 predictors of different domains (age, body mass index, echocardiographic and electrocardiographic features, laboratory measurements, comorbidities, therapies) whose relationship with the predicted risk correspond to known trends in the clinical practice. Our results suggest that prognostic models for HF in diabetic patients may improve using EHRs in combination with AI techniques for survival analysis, which provide high flexibility and better performance with respect to standard approaches.
- Published
- 2023
9. Angiotensin 1–7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro.
- Author
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Bossi, Fleur, Bernardi, Stella, De Nardo, Daniele, Bramante, Alessandra, Candido, Riccardo, Carretta, Renzo, Fischetti, Fabio, and Fabris, Bruno
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ANGIOTENSIN I , *DIABETES , *LEUCOCYTES , *ANTI-inflammatory agents , *INTRAPERITONEAL injections , *VASCULAR cell adhesion molecule-1 - Abstract
Objective Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. Methods Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion. Results Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects. Conclusions Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro . These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
10. Update on RAAS Modulation for the Treatment of Diabetic Cardiovascular Disease
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Andrea Michelli, Riccardo Candido, Giulia Zuolo, Stella Bernardi, Bruno Fabris, Bernardi, Stella, Michelli, Andrea, Zuolo, Giulia, Candido, Riccardo, and Fabris, Bruno
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0301 basic medicine ,medicine.medical_specialty ,Diabetic Cardiomyopathies ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,ACE2 ,Angiotensin-Converting Enzyme Inhibitors ,Angiotensin II Type 2 Receptor Blockers ,Review Article ,Disease ,030204 cardiovascular system & hematology ,Diabete ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Angiotensin ,0302 clinical medicine ,Endocrinology ,Diabetic cardiomyopathy ,Diabetes mellitus ,Internal medicine ,Cardiovascular Disease ,medicine ,Humans ,In patient ,Myocardial infarction ,education ,education.field_of_study ,lcsh:RC648-665 ,business.industry ,Insulin ,Diabetes ,(pro)renin ,Atherosclerosis ,medicine.disease ,AT2R ,ANP ,030104 developmental biology ,Premature atherosclerosis ,Cardiovascular Diseases ,Cardiology ,business - Abstract
Since the advent of insulin, the improvements in diabetes detection and the therapies to treat hyperglycemia have reduced the mortality of acute metabolic emergencies, such that today chronic complications are the major cause of morbidity and mortality among diabetic patients. More than half of the mortality that is seen in the diabetic population can be ascribed to cardiovascular disease (CVD), which includes not only myocardial infarction due to premature atherosclerosis but also diabetic cardiomyopathy. The importance of renin-angiotensin-aldosterone system (RAAS) antagonism in the prevention of diabetic CVD has demonstrated the key role that the RAAS plays in diabetic CVD onset and development. Today, ACE inhibitors and angiotensin II receptor blockers represent the first line therapy for primary and secondary CVD prevention in patients with diabetes. Recent research has uncovered new dimensions of the RAAS and, therefore, new potential therapeutic targets against diabetic CVD. Here we describe the timeline of paradigm shifts in RAAS understanding, how diabetes modifies the RAAS, and what new parts of the RAAS pathway could be targeted in order to achieve RAAS modulation against diabetic CVD.
- Published
- 2016
11. Angiotensin 1-7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro
- Author
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Stella Bernardi, Alessandra Bramante, Riccardo Candido, Fleur Bossi, Bruno Fabris, Daniele De Nardo, Renzo Carretta, Fabio Fischetti, Bossi, Fleur, Bernardi, Stella, DE NARDO, Daniele, Bramante, Alessandra, Candido, Riccardo, Carretta, Renzo, Fischetti, Fabio, and Fabris, Bruno
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0301 basic medicine ,Male ,030204 cardiovascular system & hematology ,Pharmacology ,Diabete ,Real-Time Polymerase Chain Reaction ,Muscle hypertrophy ,Proinflammatory cytokine ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Angiotensin ,Intravital microscopy ,0302 clinical medicine ,In vivo ,Cell Movement ,Renin–angiotensin system ,Leukocyte Trafficking ,medicine ,Leukocytes ,Animals ,Leukocyte Rolling ,Cells, Cultured ,Leukocyte-endothelial adhesion ,business.industry ,Diabetes ,Streptozotocin ,Immunohistochemistry ,Extravasation ,Peptide Fragments ,Rats ,Renin-angiotensin system ,Cardiology and Cardiovascular Medicine ,030104 developmental biology ,Gene Expression Regulation ,Immunology ,RNA ,Endothelium, Vascular ,Angiotensin I ,business ,Cell Adhesion Molecules ,medicine.drug - Abstract
Objective Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. Methods Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion. Results Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects. Conclusions Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro . These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis.
- Published
- 2015
12. Linking diabetes and atherosclerosis
- Author
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Stella Bernardi, Riccardo Candido, Terri J. Allen, Candido, Riccardo, Bernardi, Stella, and Allen, Terri J.
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hypertension ,Endocrinology, Diabetes and Metabolism ,Inflammation ,renin-angiotensin system ,diabetic dysplipidemia ,Pathogenesis ,atherosclerosi ,Diabetes mellitus ,medicine ,Endothelial dysfunction ,complement system ,Macrovascular disease ,diabetes ,business.industry ,medicine.disease ,immunity ,advance glycation end product ,Residual risk ,Blood pressure ,diabete ,inflammation ,Immunology ,medicine.symptom ,advance glycation end products ,atherosclerosis ,business ,Dyslipidemia - Abstract
Cardiovascular diseases are the major causes of morbidity and mortality in people with diabetes. Macroangiopathy in diabetes is manifested by more accelerated and progressive atherosclerosis, which is more widely distributed. The pathogenesis of this accelerated atherosclerosis is multifactorial and includes very complex interactions. Several abnormalities - such as hyperglycemia, dyslipidemia, hypertension, endothelial dysfunction, renin-angiotensin system activation and chronic subclinical inflammation - all appear to play important roles in the development of diabetes-induced atherosclerosis. Treatment of the residual risk, other than glycemia, blood pressure and low-density lipoprotein cholesterol, remains important as the rate of diabetes increases worldwide. A synergistic multifactorial approach against both conventional cardiovascular risk factors and emerging risk factors, such as vasoactive systems, the AGE-RAGE axis, novel proteins, such as TRAIL, and the complement system, as well as oxidative stress and inflammation, may be a promising way to prevent macrovascular disease in diabetes. In this review we focus on the major causes and mechanisms of atherosclerotic disease in patients with diabetes and highlight emerging targets for therapeutic intervention.
- Published
- 2009
13. Hypertension and diabetes: emphasis on the renin-angiotensin system in atherosclerosis
- Author
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Riccardo Candido, Stella Bernardi, Bruno Fabris, Candido, Riccardo, Bernardi, Stella, and Fabris, Bruno
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medicine.medical_specialty ,hypertension ,renin-angiotensin system ,Diabete ,Pathogenesis ,atherosclerosi ,Diabetes mellitus ,Internal medicine ,Diabetes ,atherosclerosis ,ACE-inhibition ,AT1 receptor blockade ,Renin–angiotensin system ,Internal Medicine ,medicine ,biology ,business.industry ,Angiotensin-converting enzyme ,medicine.disease ,Blockade ,Clinical trial ,Endocrinology ,Blood pressure ,Pathophysiology of hypertension ,biology.protein ,Cardiology ,business - Abstract
Cardiovascular diseases (CVDs) are the major causes of morbidity and mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of macrovascular complications. Hypertension is approximately twice as frequent in subjects with diabetes compared with non-diabetic patients. Furthermore, up to 75Y% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (i.e. reducing blood pressure to < 130/80 mmHg) in persons with coexistent diabetes and hypertension. Macroangiopathy in diabetes is manifested by accelerated atherosclerosis which affects heart, brain and peripheral arteries. The pathogenesis of this accelerated atherosclerosis is multifactorial and includes a very complex interaction. Several data suggest a key role for renin-angiotensin system (RAS) activation in the pathophysiology of macrovascular complications in diabetic hypertensive subjects. Consequently, RAS blockade exerts potent antiatherosclerotic effects, which are mediated by their antihypertensive, anti-inflammatory, antiproliferative, and oxidative stress lowering properties. Inhibitors of the system, ie, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are now first line treatment to prevent CVD in patients with diabetes and hypertension. In addition, recent clinical trials have suggested that RAS blockade may protect against the development of de-novo diabetes in at-risk patients. Finally, the recent identification of new components of the RAS should provide fertile territory to not only examine new targets linked to the RAS but potentially to design more rational treatments for the prevention of CVD in patients with diabetes and hypertension.
- Published
- 2009
14. Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy
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Gianni Sava, Barbara Toffoli, Laura Zorzin, Marco Stebel, Bruno Fabris, R. Candido, Moreno Cocchietto, Cocchietto, M., Zorzina, L., Toffoli, Barbara, Candido, Riccardo, Fabris, Bruno, Stebel, M., and Sava, Gianni
- Subjects
Microsphere ,Blood Glucose ,Glycation End Products, Advanced ,medicine.medical_specialty ,Oral treatment ,Biopolymer ,Endocrinology, Diabetes and Metabolism ,Capsules ,Diabetic nephropathy ,Diabete ,Nephropathy ,Diabetes Mellitus, Experimental ,Pathogenesis ,Endocrinology ,Biopolymers ,AGE ,Glycation ,Glycosuria ,Microspheres ,Microencapsulated lysozyme ,Animal model of diabetes ,Diabetes ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Albuminuria ,Animals ,Diabetic Nephropathies ,Rats, Wistar ,business.industry ,Body Weight ,General Medicine ,medicine.disease ,Streptozotocin ,Rats ,Animal model of diabete ,Microalbuminuria ,Muramidase ,business ,Kidney disease ,medicine.drug - Abstract
Aim Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. Methods LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. Results The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. Conclusion Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model.
- Published
- 2008
15. Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor
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Cristina Millevoi, Monica Bortoletto, Riccardo Candido, Moreno Bardelli, Maria Rosa Cattin, Faccini L, Renzo Carretta, Cristina Zennaro, Michele Carraro, Angela Fiorotto, Francesco Fior, Mary Artero, Bruno Fabris, Fabris, Bruno, Candido, Riccardo, Carraro, Michele, Fior, Francesco, Artero, Mary, Zennaro, Cristina, Cattin, MARIA ROSA, Fiorotto, Angela, Bortoletto, Monica, Millevoi, Cristina, Bardelli, Moreno, Faccini, Luigi, and Carretta, Renzo
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Kidney Glomerulus ,Renal function ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Peptidyl-Dipeptidase A ,Kidney ,Permeability ,Nephropathy ,Quinaprilat ,Diabetic nephropathy ,Internal medicine ,Tetrahydroisoquinolines ,Internal Medicine ,medicine ,Animals ,Diabetic Nephropathies ,ACE-inhibitor ,Rats, Wistar ,Nephroprotection ,Serum Albumin ,diabetes ,Dose-Response Relationship, Drug ,business.industry ,Body Weight ,Quinapril ,medicine.disease ,Isoquinolines ,Rats ,Endocrinology ,medicine.anatomical_structure ,diabete ,ACE inhibitor ,business ,medicine.drug ,Kidney disease - Abstract
A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (Palb) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg · kg−1 · day−1. Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of Palb in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced Palb significantly in concentration ranges from 10−6 to 10−14 mol/l compared with results in control glomeruli. The effect on Palb may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the Palb defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.
- Published
- 2001
16. Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage in hypertensive diabetic rats
- Author
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Bruno Fabris, M. Fazio, Renzo Carretta, Riccardo Candido, Moreno Bardelli, Fabio Fischetti, Lorenzo Armini, Mario Calci, L. Campanacci, Fabris, Bruno, Candido, Riccardo, Armini, L., Fischetti, Fabio, Calci, M., Bardelli, Moreno, Fazio, M., Campanacci, L., and Carretta, Renzo
- Subjects
Male ,Reserpine ,Physiology ,Renal Hypertrophy ,nephroprotection ,diabetes ,ACE-inhibition ,Sodium Chloride Symporter Inhibitors ,Hyperfiltration ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,urologic and male genital diseases ,Kidney ,Diabetic nephropathy ,Enalapril ,Rats, Inbred SHR ,Spirapril ,Diabetic Nephropathies ,Diuretics ,glomerulosclerosi ,Hydralazine ,Proteinuria ,medicine.anatomical_structure ,Hydrochlorothiazide ,Hypertension ,Disease Progression ,Drug Therapy, Combination ,Cardiology and Cardiovascular Medicine ,Glomerular hyperfiltration ,medicine.drug ,Glomerular Filtration Rate ,medicine.medical_specialty ,Renal function ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Antihypertensive Agents ,glomerulosclerosis ,urogenital system ,business.industry ,Glomerulosclerosis ,Hypertrophy ,medicine.disease ,Rats ,Endocrinology ,diabete ,business ,Diabetic Angiopathies ,Kidney disease - Abstract
Objective Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats. Design and methods Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated. Results The blood pressure reduction was equal in rats receiving either SPI or HRH. The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis. Conclusions The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis.
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