34 results on '"Rodrigues Díez, Raquel"'
Search Results
2. Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension
- Author
-
Díaz del Campo, Lucia S., García-Redondo, Ana B., Rodríguez, Cristina, Zaragoza, Carlos, Duro-Sánchez, Santiago, Palmas, Francesco, de Benito-Bueno, Angela, Socuéllamos, Paula G., Peraza, Diego A., Rodrigues-Díez, Raquel, Valenzuela, Carmen, Dalli, Jesmond, Salaices, Mercedes, and Briones, Ana M.
- Published
- 2023
- Full Text
- View/download PDF
3. CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation
- Author
-
Rodrigues-Díez, Raúl R., Tejera-Muñoz, Antonio, Esteban, Vanesa, Steffensen, Lasse B., Rodrigues-Díez, Raquel, Orejudo, Macarena, Rayego-Mateos, Sandra, Falke, Lucas L., Cannata-Ortiz, Pablo, Ortiz, Alberto, Egido, Jesus, Mallat, Ziad, Briones, Ana M., Bajo, M. Auxiliadora, Goldschmeding, Roel, and Ruiz-Ortega, Marta
- Published
- 2022
- Full Text
- View/download PDF
4. The C-terminal module IV of connective tissue growth factor is a novel immune modulator of the Th17 response
- Author
-
Rodrigues-Díez, Raquel, Rodrigues-Díez, Raúl R, Rayego-Mateos, Sandra, Suarez-Alvarez, Beatriz, Lavoz, Carolina, Stark Aroeira, Luiz, Sánchez-López, Elsa, Orejudo, Macarena, Alique, Matilde, Lopez-Larrea, Carlos, Ortiz, Alberto, Egido, Jesús, and Ruiz-Ortega, Marta
- Published
- 2013
- Full Text
- View/download PDF
5. Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
- Author
-
Ballesteros Martínez, Constanza, Rodrigues Díez, Raquel, Beltrán Romero, Luis Matías, Moreno Carriles, Rosa, Martínez Martínez, Ernesto, González Amor, María, Briones, Ana M., and Universidad de Sevilla. Departamento de Medicina
- Subjects
Inflammation ,Vascular function and remodelling ,MPGES-1 ,Adipose tissue alterations ,Obesity - Abstract
Background and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory con ditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach: mPGES-1+/+ and mPGES-1 / mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glu cose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed by myography. Histological studies, q-RT-PCR, and western blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients was correlated with vascular damage. Key Results: Male mPGES-1 / mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensi tivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared with mPGES-1+/+ mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, induced by HFD. Obesity-induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES-1 / mice. In humans, we found a positive correlation between mPGES-1 expression in abdominal fat and vascular remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers. Conclusions and Implications: mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and meta bolic alterations.
- Published
- 2022
6. Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress.
- Author
-
González-Amor, María, García-Redondo, Ana B, Jorge, Inmaculada, Zalba, Guillermo, Becares, Martina, Ruiz-Rodríguez, María J, Rodríguez, Cristina, Bermeo, Hugo, Rodrigues-Díez, Raquel, Rios, Francisco J, Montezano, Augusto C, Martínez-González, Jose, Vázquez, Jesús, Redondo, Juan Miguel, Touyz, Rhian M, Guerra, Susana, Salaices, Mercedes, and Briones, Ana M
- Subjects
ENDOTHELIUM diseases ,ANGIOTENSIN II ,OXIDATIVE stress ,CAROTID intima-media thickness ,MONONUCLEAR leukocytes - Abstract
Aims Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknown. Methods and results Bioinformatics identified ISG15 as a mediator of hypertension-associated vascular damage. ISG15 expression positively correlated with systolic and diastolic blood pressure and carotid intima-media thickness in human peripheral blood mononuclear cells. Consistently, Isg15 expression was enhanced in aorta from hypertension models and in angiotensin II (AngII)-treated vascular cells and macrophages. Proteomics revealed differential expression of proteins implicated in cardiovascular function, extracellular matrix and remodelling, and vascular redox state in aorta from AngII-infused ISG15
–/– mice. Moreover, ISG15–/– mice were protected against AngII-induced hypertension, vascular stiffness, elastin remodelling, endothelial dysfunction, and expression of inflammatory and oxidative stress markers. Conversely, mice with excessive ISGylation (USP18C61A ) show enhanced AngII-induced hypertension, vascular fibrosis, inflammation and reactive oxygen species (ROS) generation along with elastin breaks, aortic dilation, and rupture. Accordingly, human and murine abdominal aortic aneurysms showed augmented ISG15 expression. Mechanistically, ISG15 induces vascular ROS production, while antioxidant treatment prevented ISG15-induced endothelial dysfunction and vascular remodelling. Conclusion ISG15 is a novel mediator of vascular damage in hypertension through oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
7. Human iPSC-derived neural crest stem cells can produce EPO and induce erythropoiesis in anemic mice
- Author
-
Brizi, Valerio, Buttò, Sara, Cerullo, Domenico, Michele Lavecchia, Angelo, Rodrigues-Diez, Raquel, Novelli, Rubina, Corna, Daniela, Benigni, Ariela, Remuzzi, Giuseppe, and Xinaris, Christodoulos
- Published
- 2021
- Full Text
- View/download PDF
8. Pharmacological Modulation of Epithelial Mesenchymal Transition Caused by Angiotensin II. Role of ROCK and MAPK Pathways
- Author
-
Rodrigues-Díez, Raquel, Carvajal-González, Gisselle, Sánchez-López, Elsa, Rodríguez-Vita, Juan, Rodrigues Díez, Raúl, Selgas, Rafael, Ortiz, Alberto, Egido, Jesús, Mezzano, Sergio, and Ruiz-Ortega, Marta
- Published
- 2008
- Full Text
- View/download PDF
9. Microsomal prostaglandin E synthase‐1 is involved in the metabolic and cardiovascular alterations associated with obesity.
- Author
-
Ballesteros‐Martínez, Constanza, Rodrigues‐Díez, Raquel, Beltrán, Luis M., Moreno‐Carriles, Rosa, Martínez‐Martínez, Ernesto, González‐Amor, María, Martínez‐González, Jose, Rodríguez, Cristina, Cachofeiro, Victoria, Salaices, Mercedes, and Briones, Ana M.
- Subjects
- *
WHITE adipose tissue , *WEIGHT gain , *VASCULAR remodeling , *VASCULAR resistance , *ABDOMINAL adipose tissue , *PROSTAGLANDIN receptors - Abstract
Background and Purpose: Microsomal prostaglandin E synthase‐1 (mPGES‐1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory conditions. We evaluated the role of mPGES‐1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach mPGES‐1+/+ and mPGES‐1−/− mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glucose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed by myography. Histological studies, q‐RT‐PCR, and western blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients was correlated with vascular damage. Key Results: Male mPGES‐1−/− mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensitivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared with mPGES‐1+/+ mice. mPGES‐1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, induced by HFD. Obesity‐induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES‐1−/− mice. In humans, we found a positive correlation between mPGES‐1 expression in abdominal fat and vascular remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES‐1 expression and inflammatory markers. Conclusions and Implications: mPGES‐1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and metabolic alterations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Connective tissue growth factor is a new ligand of epidermal growth factor receptor
- Author
-
Rayego-Mateos, Sandra, Rodrigues-Díez, Raquel, Morgado-Pascual, Jose Luis, Rodrigues Díez, Raul R., Mas, Sebastian, Lavoz, Carolina, Alique, Matilde, Pato, Janos, Keri, Gyorgy, Ortiz, Alberto, Egido, Jesus, and Ruiz-Ortega, Marta
- Published
- 2013
- Full Text
- View/download PDF
11. Specialized Pro-Resolving Lipid Mediators: New Therapeutic Approaches for Vascular Remodeling.
- Author
-
Díaz del Campo, Lucía Serrano, Rodrigues-Díez, Raquel, Salaices, Mercedes, Briones, Ana M., and García-Redondo, Ana B.
- Subjects
- *
VASCULAR remodeling , *THERAPEUTICS , *ESSENTIAL fatty acids , *VASCULAR smooth muscle , *UNSATURATED fatty acids , *LIPIDS - Abstract
Vascular remodeling is a typical feature of vascular diseases, such as atherosclerosis, aneurysms or restenosis. Excessive inflammation is a key mechanism underlying vascular remodeling via the modulation of vascular fibrosis, phenotype and function. Recent evidence suggests that not only augmented inflammation but unresolved inflammation might also contribute to different aspects of vascular diseases. Resolution of inflammation is mediated by a family of specialized pro-resolving mediators (SPMs) that limit immune cell infiltration and initiate tissue repair mechanisms. SPMs (lipoxins, resolvins, protectins, maresins) are generated from essential polyunsaturated fatty acids. Synthases and receptors for SPMs were initially described in immune cells, but they are also present in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), where they regulate processes important for vascular physiology, such as EC activation and VSMC phenotype. Evidence from genetic models targeting SPM pathways and pharmacological supplementation with SPMs have demonstrated that these mediators may play a protective role against the development of vascular remodeling in atherosclerosis, aneurysms and restenosis. This review focuses on the latest advances in understanding the role of SPMs in vascular cells and their therapeutic effects in the vascular remodeling associated with different cardiovascular diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Special Issue "Oxidative Stress in Aging and Associated Chronic Diseases".
- Author
-
Mas-Bargues, Cristina, Alique, Matilde, Barrús-Ortiz, Mª Teresa, Borrás, Consuelo, and Rodrigues-Díez, Raquel
- Subjects
OXIDATIVE stress ,SARCOPENIA ,CHRONIC diseases ,OLDER people ,SUCCESSFUL aging ,BROWN adipose tissue - Abstract
The review describes how increased oxidative stress, cell senescence, and chronic inflammation promote cardiovascular and renal diseases as the paradigm of age-related chronic disease. They reported downregulated antioxidant levels and increased oxidative damage to lipids during aging, thereby suggesting oxidative stress as the original cause. Aging is a risk factor for several diseases, including cardiovascular disease, type 2 diabetes, hypertension, cancer, osteoarthritis, and Alzheimer; oxidative stress is a key player in the development and progression of aging and age-associated diseases. Interestingly, old mice fed with a low phosphate diet for three months showed improvement in vascular parameters, suggesting that dietary control of the phosphate intake diet could prevent premature vascular aging and delay aging-associated diseases such as vasculature aging. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
13. Supplementation with the Symbiotic Formulation Prodefen ® Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats.
- Author
-
Méndez-Albiñana, Pablo, Martínez-González, Ángel, Camacho-Rodríguez, Laura, Ferreira-Lazarte, Álvaro, Villamiel, Mar, Rodrigues-Díez, Raquel, Balfagón, Gloria, García-Redondo, Ana B., Prieto-Nieto, Mª Isabel, and Blanco-Rivero, Javier
- Subjects
MESENTERIC artery ,VASOCONSTRICTION ,NITRIC-oxide synthases ,OXIDATIVE stress ,VASCULAR resistance ,SYSTOLIC blood pressure ,HYPERTENSION - Abstract
In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen
® (108 colony forming units/day, 4 weeks). Prodefen® diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen® . Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen® , through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen® caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen® could be an interesting non-pharmacological approach to ameliorate hypertension. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
14. Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function.
- Author
-
Caracuel, Laura, Sastre, Esther, Callejo, María, Rodrigues-Díez, Raquel, García-Redondo, Ana B., Prieto, Isabel, Nieto, Carlos, Salaices, Mercedes, Aller, Ma Ángeles, Arias, Jaime, and Blanco-Rivero, Javier
- Subjects
LIVER failure ,NITRIC-oxide synthases ,HEPATIC encephalopathy ,BILE ducts ,CEREBRAL arteries - Abstract
The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F
1α releases were increased, whereas thromboxane (TX) B2 was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI2 synthase, and TXA2 S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
15. Interleukin-17A induces vascular remodeling of small arteries and blood pressure elevation.
- Author
-
Orejudo, Macarena, García-Redondo, Ana B., Rodrigues-Diez, Raúl R., Rodrigues-Díez, Raquel, Santos-Sanchez, Laura, Tejera-Muñoz, Antonio, Egido, Jesús, Selgas, Rafael, Salaices, Mercedes, Briones, Ana M., and Ruiz-Ortega, Marta
- Subjects
BLOOD pressure ,VASCULAR remodeling ,HYPERTENSION ,VASCULAR smooth muscle ,ARTERIES - Abstract
An important link exists between hypertension and inflammation. Hypertensive patients present elevated circulating levels of proinflammatory cytokines, including interleukin-17A (IL-17A). This cytokine participates in host defense, autoimmune and chronic inflammatory pathologies, and cardiovascular diseases, mainly through the regulation of proinflammatory factors. Emerging evidence also suggests that IL-17A could play a role in regulating blood pressure and end-organ damage. Here, our preclinical studies in a murine model of systemic IL-17A administration showed that increased levels of circulating IL-17A raised blood pressure induced inward remodeling of small mesenteric arteries (SMAs) and arterial stiffness. In IL-17A-infused mice, treatment with hydralazine and hydrochlorothiazide diminished blood pressure elevation, without modifying mechanical and structural properties of SMA, suggesting a direct vascular effect of IL-17A. The mechanisms of IL-17A seem to involve an induction of vascular smooth muscle cell (VSMC) hypertrophy and phenotype changes, in the absence of extracellular matrix (ECM) proteins accumulation. Accordingly, treatment with an IL-17A neutralizing antibody diminished SMA remodeling in a model of angiotensin II (Ang II) infusion. Moreover, in vitro studies in VSMCs reported here, provide further evidence of the direct effects of IL-17A on cell growth responses. Our experimental data suggest that IL-17A is a key mediator of vascular remodeling of the small arteries, which might contribute, at least in part, to blood pressure elevation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
16. Cardiovascular risk factors and oxidative stress in young people
- Author
-
Rodrigues-Díez, Raquel and Salaices, Mercedes
- Published
- 2017
- Full Text
- View/download PDF
17. TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2.
- Author
-
Rodrigues-Díez, Raquel, Rayego-Mateos, Sandra, Orejudo, Macarena, Aroeira, Luiz Stark, Selgas, Rafael, Ortiz, Alberto, Egido, Jesús, and Ruiz-Ortega, Marta
- Subjects
- *
KIDNEY disease treatments , *TRANSFORMING growth factors-beta , *INFLAMMATION , *CONNECTIVE tissue growth factor , *BIOMARKERS , *CYTOKINES - Abstract
The CCN family member 2 (CCN2, also known as connective tissue growth factor) may behave as a risk biomarker and a potential therapeutic target for renal disease. CCN2 participates in the regulation of inflammation and fibrosis. TGF-β is considered the main fibrogenic cytokine; however, in some pathological settings TGF-β also has anti-inflammatory properties. CCN2 has been proposed as a downstream profibrotic mediator of TGF-β, but data on TGF-β role in CCN2 actions are scarce. Our aim was to evaluate the effect of TGF-β blockade in CCN2-mediated experimental renal damage. Systemic administration of the C-terminal module of CCN2 to mice caused sustained renal inflammation. In these mice, TGF-β blockade, using an anti-TGF-β neutralizing antibody, significantly increased renal expression of the NGAL (a kidney injury biomarker), kidney infiltration by monocytes/macrophages, and upregulation of MCP-1 expression. The anti-inflammatory effect of TGF-β seems to be mediated by a dysregulation of the systemic Treg immune response, shown by decreased levels of circulating CD4+/Foxp3+Treg cells. Our experimental data support the idea that TGF-β exerts anti-inflammatory actions in the kidney and suggest that it is not an optimal therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
18. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage.
- Author
-
Liappas, Georgios, Gónzalez-Mateo, Guadalupe Tirma, Majano, Pedro, Sánchez- Tomero, José Antonio, Ruiz-Ortega, Marta, Rodrigues Díez, Raquel, Martín, Pilar, Sanchez-Díaz, Raquel, Selgas, Rafael, López-Cabrera, Manuel, and Aguilera Peralta, Abelardo
- Subjects
TREATMENT of chronic kidney failure ,BIOMARKERS ,NONSTEROIDAL anti-inflammatory agents ,PERITONEAL dialysis ,PERITONEUM ,PERITONEUM diseases ,T cells ,CYCLOOXYGENASE 2 ,FIBROSIS ,DISEASE risk factors - Abstract
Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
19. Regulation of Vascular and Renal Cells by Common Mediators in Health and Disease: Role of the Renin–Angiotensin System in the Pathophysiology of Hypertension and Cardiovascular Disease.
- Author
-
Ruiz-Ortega, Marta, Rodrigues-Díez, Raquel, Rayego, Sandra, Rodrigues-Díez, Raul R., Lavoz, Carolina, Civantos, Esther, Carvajal, Gisselle, Mezzano, Sergio, Ortiz, Alberto, and Egido, Jesus
- Abstract
In the classic view of the renin angiotensin system (RAS), angiotensin II (AngII) is the main effector peptide. Circulating RAS regulates physiological responses, whereas the local RAS is activated during tissue injury and contributes to pathological processes, including cell proliferation/apoptosis, fibrosis, and inflammation. AngII has direct effects on these processes through activation of mitogen-activated protein kinase (MAPKs) and Smad and nuclear factor kappa B (NF-ΚB) transcription factors. In addition, AngII recruits important secondary mediators, such as transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), and chemokines. AngII binds to the angiotensin type 1 and 2 (AT
1 and AT2 ) receptors mediating different cellular responses. Both angiotensin-converting enzyme (ACE) inhibitors and AngII receptor antagonists (ARA II, targeting the AT1 receptor) have demonstrated their therapeutic efficacy in protecting the cardiovascular system and kidneys in humans. Some AngII degradation peptides are also biologically active. Aminopeptidases promote the generation of AngIII and AngIV, two N-terminal degradation products, whereas ACE-2 catalyzes generation of Ang-(1–7). AngIV has been reported to bind to the AngIV-binding-site insulinregulated aminopeptidase (IRAP) and to promote inflammation in vascular cells. Ang-(1–7) activation of the Mas receptor may be beneficial in vascular injury but increases kidney inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
20. IL-17A is a novel player in dialysis-induced peritoneal damage.
- Author
-
Rodrigues-Díez, Raquel, Aroeira, Luiz S, Orejudo, Macarena, Bajo, M-Auxiliadora, Heffernan, José Jiménez, Rodrigues-Díez, Raúl R, Rayego-Mateos, Sandra, Ortiz, Alberto, Gonzalez-Mateo, Guadalupe, López-Cabrera, Manuel, Selgas, Rafael, Egido, Jesús, and Ruiz-Ortega, Marta
- Subjects
- *
PERITONEAL dialysis , *T helper cells , *GLOMERULONEPHRITIS , *GENE expression , *FIBROSIS , *CYTOKINES - Abstract
The classical view of the immune system has changed by the discovery of novel T-helper (Th) subsets, including Th17 (IL-17A-producing cells). IL-17A participates in immune-mediated glomerulonephritis and more recently in inflammatory pathologies, including experimental renal injury. Peritoneal dialysis patients present chronic inflammation and Th1/Th2 imbalance, but the role of the Th17 response in peritoneal membrane damage has not been investigated. In peritoneal biopsies from dialyzed patients, IL-17A immunostaining was found mainly in inflammatory areas and was absent in the healthy peritoneum. IL-17A-expressing cells included lymphocytes (CD4+ and γδ), neutrophils, and mast cells. Elevated IL-17A effluent concentrations were found in long-term peritoneal dialysis patients. Studies in mice showed that repeated exposure to recombinant IL-17A caused peritoneal inflammation and fibrosis. Moreover, chronic exposure to dialysis fluids resulted in a peritoneal Th17 response, including elevated IL-17A gene and protein production, submesothelial cell infiltration of IL-17A-expressing cells, and upregulation of Th17 differentiation factors and cytokines. IL-17A neutralization diminished experimental peritoneal inflammation and fibrosis caused by chronic exposure to dialysis fluids in mice. Thus, IL-17A is a key player of peritoneum damage and it may be a good candidate for therapeutic intervention in peritoneal dialysis patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
21. Integrin-linked kinase plays a key role in the regulation of angiotensin II-induced renal inflammation.
- Author
-
ALIQUE, Matilde, CIVANTOS, Esther, SANCHEZ-LOPEZ, Elsa, LAVOZ, Carolina, RAYEGO-MATEOS, Sandra, RODRIGUES-DÍEZ, Raquel, GARCÍA-REDONDO, Ana Belén, EGIDO, Jesús, ORTIZ, Alberto, RODRÍGUEZ-PUYOL, Diego, RODRÍGUEZ-PUYOL, Manuel, and RUIZ-ORTEGA, Marta
- Subjects
KIDNEY disease treatments ,INTEGRIN-linked kinase ,ANGIOTENSIN II ,NF-kappa B ,INFLAMMATION treatment ,CHEMOKINES ,PROTEIN kinase B - Abstract
ILK (integrin-linked kinase) is an intracellular serine/threonine kinase involved in cell-matrix interactions. ILK dysregulation has been described in chronic renal disease and modulates podocyte function and fibrosis, whereas data about its role in inflammation are scarce. AngII (angiotensin II) is a pro-inflammatory cytokine that promotes renal inflammation. AngII blockers are renoprotective and down-regulate ILK in experimental kidney disease, but the involvement of ILK in the actions of AngII in the kidney has not been addressed. Therefore we have investigated whether ILK signalling modulates the kidney response to systemic AngII infusion in wild-type and ILK-conditional knockout mice. In wild-type mice, AngII induced an inflammatory response, characterized by infiltration of monocytes/macrophages and lymphocytes, and up-regulation of pro-inflammatory factors (chemokines, adhesion molecules and cytokines). AngII activated several intracellular signalling mechanisms, such as the NF-κB (nuclear factor κB) transcription factor, Akt and production of ROS (reactive oxygen species). All these responses were prevented in AngII-infused ILK-deficient mice. In vitro studies characterized further the mechanisms regulating the inflammatory response modulated by ILK. In cultured tubular epithelial cells ILK blockade, by siRNA, inhibited AngII-induced NF-κB subunit p65 phosphorylation and its nuclear translocation. Moreover, ILK gene silencing prevented NF-κB-related pro-inflammatory gene up-regulation. The results of the present study demonstrate that ILK plays a key role in the regulation of renal inflammation by modulating the canonical NF-κB pathway, and suggest a potential therapeutic target for inflammatory renal diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
22. Statins Inhibit Angiotensin II/Smad Pathway and Related Vascular Fibrosis, by a TGF-β-Independent Process.
- Author
-
Rodrigues^Díez, Raúl, Rodrigues-Díez, Raquel, Lavoz, Carolina, Rayego-Mateos, Sandra, Civantos, Esther, Rodríguez-Vita, Juan, Mezzano, Sergio, Ortiz, Alberto, Egido, Jesús, and Ruiz-Ortega, Marta
- Subjects
- *
STATINS (Cardiovascular agents) , *ANGIOTENSIN II , *FIBROSIS , *ATHEROSCLEROSIS , *TRANSFORMING growth factors , *BLOOD circulation disorders - Abstract
We have recently described that in an experimental model of atherosclerosis and in vascular smooth muscle cells (VSMCs) statins increased the activation of the Smad pathway by transforming growth factor-β (TGF-β), leading to an increase in TGF-β-dependent matrix accumulation and plaque stabilization. Angiotensin II (AngII) activates the Smad pathway and contributes to vascular fibrosis, although the in vivo contribution of TGF-β has not been completely elucidated. Our aim was to further investigate the mechanisms involved in AngII-induced Smad activation in the vasculature, and to clarify the beneficial effects of statins on AngII-induced vascular fibrosis. Infusion of AngII into rats for 3 days activates the Smad pathway and increases fibrotic-related factors, independently of TGF-β, in rat aorta. Treatment with atorvastatin or simvastatin inhibited AngII-induced Smad activation and related-fibrosis. In cultured rat VSMCs, direct AngII/Smad pathway activation was mediated by p38 MAPK and ROCK activation. Preincubation of VSMCs with statins inhibited AngII-induced Smad activation at all time points studied (from 20 minutes to 24 hours). All these data show that statins inhibited several AngII-activated intracellular signaling systems, including p38-MAPK and ROCK, which regulates the AngII/Smad pathway and related profibrotic factors and matrix proteins, independently of TGF-β responses. The inhibitory effect of statins on the AngII/Smad pathway could explain, at least in part, their beneficial effects on hypertension-induced vascular damage. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
23. Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation.
- Author
-
Rodríguez-Vita, Juan, Sánchez-Galán, Eva, Santamaría, Beatriz, Sánchez-López, Elsa, Rodrigues-Díez, Raquel, Blanco-Colio, Luís Miguel, Egido, Jesús, Ortiz, Alberto, and Ruiz-Ortega, Marta
- Subjects
SMOOTH muscle ,STATINS (Cardiovascular agents) ,INFLAMMATION ,CELLULAR control mechanisms ,GROWTH factors ,CARDIOVASCULAR diseases ,APOPTOSIS ,SERUM ,ATHEROSCLEROSIS - Abstract
Background: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-β (TGF-β) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-β/Smad pathway in atherosclerosis and vascular cells. Methodology: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGFβ. In addition, statins upregulated TGF-β receptor type II (TRII), and increased TGF-β synthesis and TGF-β/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-β induced apoptosis and increased TGF-β-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-β/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. Conclusions: Statins enhance TGF-β/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-β/Smad pathway is essential for statins-dependent actions in VSMCs. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
24. HMG-CoA reductase inhibitors decrease angiotensin II-induced vascular fibrosis: role of RhoA/ROCK and MAPK pathways.
- Author
-
Rupérez, Mónica, Rodriguez-Díez, Raquel, Blanco-Colio, Blanco, Sánchez-López, Elsa, Rodríguez-Vita, Juan, Esteban, Vanesa, Carvajal, Gisselle, Plaza, Juan José, Egido, Jesús, Ruiz-Ortega, Marta, Rupérez, Mónica, Rodrigues-Díez, Raquel, Blanco-Colio, Luis Miguel, Sánchez-López, Elsa, Rodríguez-Vita, Juan, Plaza, Juan José, and Egido, Jesús
- Abstract
3-Hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) present beneficial effects in cardiovascular diseases. Angiotensin II (Ang II) contributes to cardiovascular damage through the production of profibrotic factors, such as connective tissue growth factor (CTGF). Our aim was to investigate whether HMG-CoA reductase inhibitors could modulate Ang II responses, evaluating CTGF expression and the mechanisms underlying this process. In cultured vascular smooth muscle cells (VSMCs) atorvastatin and simvastatin inhibited Ang II-induced CTGF production. The inhibitory effect of statins on CTGF upregulation was reversed by mevalonate and geranylgeranylpyrophosphate, suggesting that RhoA inhibition could be involved in this process. In VSMCs, statins inhibited Ang II-induced Rho membrane localization and activation. In these cells Ang II regulated CTGF via RhoA/Rho kinase activation, as shown by inhibition of Rho with C3 exoenzyme, RhoA dominant-negative overexpression, and Rho kinase inhibition. Furthermore, activation of p38MAPK and JNK, and redox process were also involved in Ang II-mediated CTGF upregulation, and were downregulated by statins. In rats infused with Ang II (100 ng/kg per minute) for 2 weeks, treatment with atorvastatin (5 mg/kg per day) diminished aortic CTGF and Rho activation without blood pressure modification. Rho kinase inhibition decreased CTGF upregulation in rat aorta, mimicking statin effect. CTGF is a vascular fibrosis mediator. Statins diminished extracellular matrix (ECM) overexpression caused by Ang II in vivo and in vitro. In summary, HMG-CoA reductase inhibitors inhibit several intracellular signaling systems activated by Ang II (RhoA/Rho kinase and MAPK pathways and redox process) involved in the regulation of CTGF. Our results may explain, at least in part, some beneficial effects of statins in cardiovascular diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
25. Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue.
- Author
-
González-Amor, María, Vila-Bedmar, Rocío, Rodrigues-Díez, Raquel, Moreno-Carriles, Rosa, Arcones, Alba C., Cruces-Sande, Marta, Salaices, Mercedes, Mayor, Federico, Briones, Ana M., and Murga, Cristina
- Subjects
ENDOTHELIUM diseases ,ADIPOSE tissues ,INFLAMMATION ,ABDOMINAL aortic aneurysms ,G protein coupled receptors ,HIGH-fat diet ,LEPTIN - Abstract
Perivascular adipose tissue (PVAT) is increasingly being regarded as an important endocrine organ that directly impacts vessel function, structure, and contractility in obesity-associated diseases. We uncover here a role for myeloid G protein-coupled receptor kinase 2 (GRK2) in the modulation of PVAT-dependent vasodilation responses. GRK2 expression positively correlates with myeloid- (CD68) and lymphoid-specific (CD3, CD4, and CD8) markers and with leptin in PVAT from patients with abdominal aortic aneurysms. Using mice hemizygous for GRK2 in the myeloid lineage (LysM-GRK2
+/− ), we found that GRK2 deficiency in myeloid cells allows animals to preserve the endothelium-dependent acetylcholine or insulin-induced relaxation, which is otherwise impaired by PVAT, in arteries of animals fed a high fat diet (HFD). Downregulation of GRK2 in myeloid cells attenuates HFD-dependent infiltration of macrophages and T lymphocytes in PVAT, as well as the induction of tumor necrosis factor-α (TNFα) and NADPH oxidase (Nox)1 expression, whereas blocking TNFα or Nox pathways by pharmacological means can rescue the impaired vasodilator responses to insulin in arteries with PVAT from HFD-fed animals. Our results suggest that myeloid GRK2 could be a potential therapeutic target in the development of endothelial dysfunction induced by PVAT in the context of obesity. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
26. Beneficial Effect of a Multistrain Synbiotic Prodefen® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A.
- Author
-
Llévenes, Pablo, Rodrigues-Díez, Raquel, Cros-Brunsó, Laia, Prieto, Mᵃ Isabel, Casaní, Laura, Balfagón, Gloria, and Blanco-Rivero, Javier
- Abstract
A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen
® Plus. MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
27. Corrigendum to “T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage”.
- Author
-
Liappas, Georgios, Gónzalez-Mateo, Guadalupe Tirma, Majano, Pedro, Sánchez-Tomero, José Antonio, Ruiz-Ortega, Marta, Rodrigues Díez, Raquel, Martín, Pilar, Sanchez-Díaz, Raquel, Selgas, Rafael, López-Cabrera, Manuel, and Aguilera Peralta, Abelardo
- Subjects
T cells ,PERITONEUM ,MATHEMATICAL models ,PERITONEAL dialysis ,THEORY ,WOUNDS & injuries ,PHYSIOLOGY - Published
- 2017
- Full Text
- View/download PDF
28. Hypothyroidism confers tolerance to cerebral malaria.
- Author
-
Rodriguez-Muñoz, Diego, Sánchez, Ángela, Pérez-Benavente, Susana, Contreras-Jurado, Constanza, Montero-Pedrazuela, Ana, Toledo-Castillo, Marta, Gutiérrez-Hernández, María, Rodrigues-Díez, Raquel, Folgueira, Cintia, Briones, Ana M., Sabio, Guadalupe, Monedero-Cobeta, Ignacio, Chávez-Coira, Irene, Castejón, David, Fernández-Valle, Encarnación, Regadera, Javier, Bautista, José M., Aranda, Ana, and Alemany, Susana
- Subjects
- *
BLOOD-brain barrier , *THYROID hormone regulation , *CEREBRAL malaria , *GRANZYMES , *HYPOTHYROIDISM - Abstract
The article offers information about the modulation of the host's metabolism to protect tissue from damage induces tolerance to infections increasing survival. It examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria, along with mentions that hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism.
- Published
- 2022
- Full Text
- View/download PDF
29. Angiotensin II activates the Smad pathway during epithelial mesenchymal transdifferentiation.
- Author
-
Carvajal, Gisselle, Rodríguez-Vita, Juan, Rodrigues-Díez, Raquel, Sánchez-López, Elsa, Rupérez, Mónica, Cartier, Cecile, Esteban, Vanesa, Ortiz, Alberto, Egido, Jesús, Mezzano, Sergio A., and Ruiz-Ortega, Marta
- Subjects
- *
ANGIOTENSIN II , *EPITHELIAL cells , *RATS , *TRANSFORMING growth factors , *GENETIC transcription - Abstract
Epithelial to mesenchymal transdifferentiation is a novel mechanism that promotes renal fibrosis and here we investigated whether known causes of renal fibrosis (angiotensin II and transforming growth factor β, TGFβ) act through this pathway. We infused angiotensin II into rats for 1 day and found that it activated the Smad pathway which persisted for up to 2 weeks in chronically infused rats. Renal TGF-β mRNA expression was increased at 3 days and its protein at 2 weeks suggesting Smad pathway activation occurred earlier than TGF-β upregulation. In cultured human tubuloepithelial cells, angiotensin II caused a rapid activation of Smad signaling independent of TGF-β however, Smad-dependent transcription after 1 day was TGF-β mediated. Two weeks of angiotensin II infusion activated genes associated with epithelial mesenchymal transdifferentiation. Stimulation with angiotensin II for 3 days caused transdifferentiation of the cultured epithelial cells by TGF-β-mediated processes; however, early changes were independent of endogenous TGF-β. Smad7 overexpression, which blocks Smad2/3 activation, diminished angiotensin II-induced epithelial mesenchymal transdifferentiation. Our results show that angiotensin II activates the Smad signaling system by TGF-β-independent processes, in vivo and in vitro, causing renal fibrosis.Kidney International (2008) 74, 585–595; doi:10.1038/ki.2008.213; published online 28 May 2008 [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
30. A new procedure to induce aortic aneurysms in mice.
- Author
-
Rodrigues-Díez R, Tejera-Muñoz A, and Rodrigues-Diez RR
- Subjects
- Animals, Mice, Connective Tissue Growth Factor metabolism, Connective Tissue Growth Factor genetics, Angiotensin II metabolism, Angiotensin II pharmacology, Mice, Knockout, Aortic Aneurysm pathology, Aortic Aneurysm genetics, Aortic Aneurysm metabolism, Aortic Aneurysm etiology, Disease Models, Animal
- Abstract
Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage, to its rupture. Despite important advances in the surgical treatment of aortic aneurysms, there is currently no pharmacological intervention that prevents their development, reduces their expansion, or avoids their rupture. In addition to classic risk factors such age or gender, several heritable connective tissue disorders have been associated with AA developing, highlighting the role of extracellular matrix (ECM) genes alterations in the developing of AA. In this sense, we have recently demonstrated that global deletion of the cellular communicating network factor 2 (CCN2), previously known as connective tissue growth factor (CTGF) due to its role in the extracellular matrix formation, predisposes to early and lethal AAs development after Angiotensin II (Ang II) infusion in mice. Here, we detail the protocol to induce and detect AAs generation in inducible global CCN2 knockout mice after Ang II infusion which allow the characterization of CCN role in AA development and may help to the development of pharmacological target for AA treatment., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
31. Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome.
- Author
-
Mas-Bargues C, Alique M, Barrús-Ortiz MT, Borrás C, and Rodrigues-Díez R
- Abstract
The incidence of age associated chronic diseases has increased in recent years. Although several diverse causes produce these phenomena, abundant evidence shows that oxidative stress plays a central role. In recent years, numerous studies have focused on elucidating the role of oxidative stress in the development and progression of both aging and chronic diseases, opening the door to the discovery of new underlying mechanisms and signaling pathways. Among them, senolytics and senomorphics, and extracellular vesicles offer new therapeutic strategies to slow the development of aging and its associated chronic diseases by decreasing oxidative stress. In this review, we aim to discuss the role of extracellular vesicles in human cardiorenal syndrome development and their possible role as biomarkers, targets, or vehicles of drugs to treat this syndrome.
- Published
- 2021
- Full Text
- View/download PDF
32. Beneficial Effect of a Multistrain Synbiotic Prodefen ® Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A.
- Author
-
Llévenes P, Rodrigues-Díez R, Cros-Brunsó L, Prieto MI, Casaní L, Balfagón G, and Blanco-Rivero J
- Subjects
- Animals, Blood Pressure physiology, Blood Vessels enzymology, Body Weight, Diet, High-Fat, Dietary Supplements, Disease Models, Animal, Hypertension enzymology, Hypertension etiology, Hypertension physiopathology, Insulin Resistance, Male, Metabolic Syndrome etiology, Metabolic Syndrome physiopathology, Probiotics administration & dosage, Rats, Rats, Wistar, Blood Vessels physiopathology, Cyclic AMP-Dependent Protein Kinases physiology, Metabolic Syndrome enzymology, Nitric Oxide Synthase physiology, Synbiotics administration & dosage
- Abstract
A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen
® Plus . MtS was induced by HFD (45%) in male Wistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not affect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS.- Published
- 2020
- Full Text
- View/download PDF
33. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB.
- Author
-
Sánchez-López E, Rayego S, Rodrigues-Díez R, Rodriguez JS, Rodrigues-Díez R, Rodríguez-Vita J, Carvajal G, Aroeira LS, Selgas R, Mezzano SA, Ortiz A, Egido J, and Ruiz-Ortega M
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cell Line, Cells, Cultured, Chemokines metabolism, Cytokines metabolism, Disease Models, Animal, Epithelial Cells drug effects, Epithelial Cells metabolism, Epithelial Cells pathology, Inflammation metabolism, Kidney Tubules drug effects, Kidney Tubules metabolism, Macrophages drug effects, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase Kinases metabolism, NF-kappa B antagonists & inhibitors, Sesquiterpenes pharmacology, Signal Transduction drug effects, T-Lymphocytes drug effects, Cell Movement drug effects, Connective Tissue Growth Factor pharmacology, Inflammation pathology, Kidney Tubules pathology, Macrophages pathology, NF-kappa B metabolism, T-Lymphocytes pathology
- Abstract
Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway.
- Published
- 2009
- Full Text
- View/download PDF
34. Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.
- Author
-
Rodríguez-Vita J, Sánchez-Galán E, Santamaría B, Sánchez-López E, Rodrigues-Díez R, Blanco-Colio LM, Egido J, Ortiz A, and Ruiz-Ortega M
- Subjects
- Animals, Anticholesteremic Agents pharmacology, Anticholesteremic Agents therapeutic use, Apolipoproteins E genetics, Apoptosis drug effects, Atherosclerosis pathology, Atherosclerosis prevention & control, Atorvastatin, Cells, Cultured, Heptanoic Acids pharmacology, Heptanoic Acids therapeutic use, Male, Mice, Mice, Knockout, Models, Biological, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Muscle, Smooth, Vascular physiology, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology, Myocytes, Smooth Muscle physiology, Pyrroles pharmacology, Pyrroles therapeutic use, Rats, Rats, Sprague-Dawley, Signal Transduction drug effects, Signal Transduction physiology, Smad Proteins metabolism, Transforming Growth Factor beta metabolism, rho-Associated Kinases physiology, rhoA GTP-Binding Protein physiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Muscle, Smooth, Vascular drug effects, Myocytes, Smooth Muscle drug effects, Smad Proteins physiology, Transforming Growth Factor beta physiology
- Abstract
Background: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells., Methodology: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected., Conclusions: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.
- Published
- 2008
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.