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

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127

作者：

L Ren，N Liu，H Zhi，Y Li，Z Sheng

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摘要：

p pBackground/p pThe 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./p pObjective/p pTo investigate the actions of the renin-angiotensin system in vascular protection mediated by activation of PPARγ in vivo and in vitro./p pMethods/p pRats 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./p pResults/p pAfter 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 (ATsub1/subR) and up-regulated expression of angiotensin type 2 receptor (ATsub2/subR) in the aortic tissues and ANG II-treated VSMCs./p pConclusions/p pThe 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 vivo. These vasculoprotective effects of rosiglitazone were mediated at least partially by reduction in local tissue ANG II concentration, down-regulation of ATsub1/subR expression and up-regulation of ATsub2/subR expression both at the mRNA and protein levels./p

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关键词：

Macaque Granulosa cells Glucose Glycolysis Luteinization

DOI：

10.1186/1475-2840-10-10

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年份：

2011