Atorvastatin and sildenafil decrease vascular TGF-β levels and MMP-2 activity and ameliorate arterial remodeling in a model of renovascular hypertension

Redox Biology
Danielle GuimaraesJosé Eduardo Tanus-Santos

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 i...Continue Reading

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Citations

Mar 25, 2017·Expert Opinion on Therapeutic Targets·Lucas C PinheiroMichele M Castro
Jan 23, 2016·Human & Experimental Toxicology·Lais Salles de AlmeidaThiago Melo Costa Pereira
Jun 22, 2019·Current Vascular Pharmacology·Xiaoxue LiHui Huang
Dec 10, 2019·Journal of Immunology Research·Caitlin V LewisBarbara K Kemp-Harper
Mar 28, 2020·Scientific Reports·Nabarun ChakrabortySanchita P Ghosh
Sep 30, 2020·Immunopharmacology and Immunotoxicology·Asmaa Ramadan Abdel-SattarAmira M Aboyoussef
Jan 10, 2020·Journal of Immunology Research·Michał ZychRadoslaw Zagozdzon
Sep 30, 2018·Life Sciences·Petrus Pires MarquesFlávia Da Ré Guerra

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Methods Mentioned

BETA
scintillation spectroscopy
light microscopy
protein assay
electrophoresis

Software Mentioned

ImageJ
GraphPad Prism

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