ArticleRedox biology2015
Atorvastatin and sildenafil decrease vascular TGF-β levels and MMP-2 activity and ameliorate arterial remodeling in a model of renovascular hypertension.
Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The Roles of Genetic Factors in Kawasaki Disease: A Systematic Review and Meta-analysis of Genetic Association Studies.Pediatric cardiology · 2018Pooled it
- Hepatocyte growth factor blocks epithelial-mesenchymal transition and fibrosis of ureteral epithelial cells in UPJO.BMC pediatrics · 2026Article
- The Role of TGF-β Signaling in Saphenous Vein Graft Failure after Peripheral Arterial Disease Bypass Surgery.International journal of molecular sciences · 2023Review
- The effect of lipid-lowering therapies on the pro-inflammatory and anti-inflammatory properties of vascular endothelial cells.PloS one · 2023Article
- Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-β1/Smad2/3 Pathway.Current cancer drug targets · 2023Article
- Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations.Biomolecules · 2021Review
- microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation.Scientific reports · 2020Article
- Article
- Distinct Redox Signalling following Macrophage Activation Influences Profibrotic Activity.Journal of immunology research · 2019Article
- Sildenafil Citrate Influences Production of TNF-Journal of immunology research · 2019Article
- Urinary TGF-β1 was not independently associated with renal function in diabetes mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018Article
- Redox Changes in Amateur Race Car Drivers Before and After Racing.Sports medicine international open · 2017Article
- Telmisartan improves vascular remodeling through ameliorating prooxidant and profibrotic mechanisms in hypertension via the involvement of transforming growth factor-β1.Molecular medicine reports · 2017Article
- Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats.Scientific reports · 2016Article
- Tempol improves xanthine oxidoreductase-mediated vascular responses to nitrite in experimental renovascular hypertension.Redox biology · 2016Article
- Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imbalanced matrix metalloproteinase (MMP)-2 activity and transforming growth factor expression (TGF-β) are involved in vascular remodeling of hypertension. Atorvastatin and sildenafil exert antioxidant and pleiotropic effects that may result in cardiovascular protection. We hypothesized that atorvastatin and sildenafil alone or in association exert antiproliferative effects by down-regulating MMP-2 and TGF-β, thus reducing the vascular hypertrophy induced by two kidney, one clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral atorvastatin 50 mg/kg, sildenafil 45 mg/kg, or both, daily for 8 weeks. Blood pressure was monitored weekly. Morphologic changes in the aortas were studied. TGF-β levels were determined by immunofluorescence. MMP-2 activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence. The effects of both drugs on proliferative responses of aortic smooth muscle cells to PDGF and on on MMP-2 activity in vitro were determined. Atorvastatin, sildenafil, or both drugs exerted antiproliferative effects in vitro. All treatments attenuated 2K1C-induced hypertension and prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats. Aortas from 2K1C rats showed higher collagen deposition, TGF-β levels and MMP-2 activity and expression when compared with Sham-operated animals. Treatment with atorvastatin and/or sildenafil was associated with attenuation of 2K1C hypertension-induced increases in these pro-fibrotic factors. However, these drugs had no in vitro effects on hr-MMP-2 activity. Atorvastatin and sildenafil was associated with decreased vascular TGF-β levels and MMP-2 activity in renovascular hypertensive rats, thus ameliorating the vascular remodeling. These novel pleiotropic effects of both drugs may translate into protective effects in patients.
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