Vasculoprotective effects of rosiglitazone through modulating renin-angiotensin system in vivo and vitro

• Published in: Cardiovascular diabetology 2011-01, Vol.10 (1), p.10-10
• Main Authors: Ren, Liqun, Liu, Naifeng, Zhi, Hong, Li, Yingjuan, Li, Yanzhi, Tang, Rining, Sheng, Zulong
• Format: Article
• Language: English
• Subjects: Angiotensin II - blood; Animals; Aortic Diseases - etiology; Aortic Diseases - metabolism; Aortic Diseases - pathology; Aortic Diseases - prevention & control; Atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Blotting, Western; Cardiovascular Agents - pharmacology; Cell Proliferation - drug effects; Cells, Cultured; Cholesterol; Coronary vessels; Disease Models, Animal; Dose-Response Relationship, Drug; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Immunohistochemistry; Ligands; Lipids; Lipids - blood; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Original Investigation; PPAR gamma - agonists; PPAR gamma - metabolism; Radioimmunoassay; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - drug effects; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - drug effects; Receptor, Angiotensin, Type 2 - genetics; Receptor, Angiotensin, Type 2 - metabolism; Regulation; Renin-Angiotensin System - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Rodents; Smooth muscle; Studies; Thiazolidinediones - pharmacology; Time Factors
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/1475-2840-10-10

The peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone has been suggested to exert cardiovascular protection through the improvement of lipid metabolism, anti-inflammation, anti-proliferation etc. However, whether renin-angiotensin system (RAS) is involved in the vascular protective effects of PPARγ agonists is not fully understood. The present study aimed to investigate the effects of the renin-angiotensin system in vascular protection mediated by PPARγ agonists. To investigate the actions of the renin-angiotensin system in vascular protection mediated by activation of PPARγ in vivo and in vitro. Rats were fed a regular diet (n = 8), a cholesterol-rich diet plus methylthiouracil (80 mg/Kg/day, n = 10), a cholesterol-rich diet plus methylthiouracil and rosiglitazone (4 mg/kg/day, n = 10). The rosiglitazone treatment was started from one month after the start of cholesterol-rich diet plus methylthiouracil, and lasted five months. Cultured vascular smooth muscle cells (VSMCs) were pretreated with 1 μmol/L angiotensin II (ANG II) for 6 h and randomly divided into the control group; the ANG II group (1 μmol/L ANG II); the groups respectively treated with different concentration rosiglitazone (20, 30, 50) μmol/L for 12 h; the groups treated with 30 μmol/L rosiglitazone for (6, 12, 24) h. Morphology changes of the aortic tissues were observed by hematoxylin and eosin stain. The VSMC growth was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Angiotensin II and expression of angiotensin receptors were determined by radioimmunoassay, reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. After 6 months, lipid deposition, VSMC proliferation and migration toward intima were observed in aortic tissues in the rats on a cholesterol-rich diet plus methylthiouracil, while these pathological changes induced by the cholesterol-rich diet were significantly suppressed by rosiglitazone. In addition, VSMC proliferation induced by ANG II was markedly inhibited by rosiglitazone. Rosiglitazone markedly down-regulated expression of angiotensin type 1 receptor (AT1R) and up-regulated expression of angiotensin type 2 receptor (AT2R) in the aortic tissues and ANG II-treated VSMCs. The present study demonstrated that PPARγ agonist rosiglitazone suppressed ANG II-induced VSMC proliferation in vitro and early atherosclerotic formation evoked by cholesterol-rich diet in vi