Telmisartan Exerts Antiatherosclerotic Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Macrophages

被引：49

作者：

Matsumura, Takeshi ^{[1
]}

Kinoshita, Hiroyuki ^{[1
]}

Ishii, Norio ^{[1
]}

Fukuda, Kazuki ^{[1
]}

Motoshima, Hiroyuki ^{[1
]}

Senokuchi, Takafumi ^{[1
]}

Taketa, Kayo ^{[1
]}

Kawasaki, Shuji ^{[1
]}

Nishimaki-Mogami, Tomoko ^{[2
]}

Kawada, Teruo ^{[3
]}

Nishikawa, Takeshi ^{[1
]}

Araki, Eiichi ^{[1
]}

机构：

[1] Kumamoto Univ, Fac Life Sci, Dept Metab Med, Kumamoto 8608556, Japan

[2] Natl Inst Hlth Sci, Dept Biochem & Metab, Setagaya Ku, Tokyo, Japan

[3] Kyoto Univ, Nutr Chem Lab, Div Food Sci & Biotechnol, Grad Sch Agr, Kyoto, Japan

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2011年 / 31卷 / 06期

基金：

日本学术振兴会;

关键词：

atherosclerosis; hypertension; macrophages; vascular biology; peroxisome proliferator-activated receptor; LOW-DENSITY-LIPOPROTEIN; E-DEFICIENT MICE; COLONY-STIMULATING FACTOR; AMELIORATES INSULIN-RESISTANCE; CONVERTING-ENZYME-INHIBITOR; RENIN-ANGIOTENSIN SYSTEM; PPAR-GAMMA; ATHEROSCLEROTIC LESIONS; HYPERTENSIVE PATIENTS; CELL-PROLIFERATION;

D O I：

10.1161/ATVBAHA.110.222067

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective-Telmisartan, an angiotensin type I receptor blocker (ARB), protects against the progression of atherosclerosis. Here, we investigated the molecular basis of the antiatherosclerotic effects of telmisartan in macrophages and apolipoprotein E-deficient mice. Methods and Results-In macrophages, telmisartan increased peroxisome proliferator-activated receptor-gamma (PPAR gamma) activity and PPAR ligand-binding activity. In contrast, 3 other ARBs, losartan, valsartan, and olmesartan, did not affect PPAR gamma activity. Interestingly, high doses of telmisartan activated PPAR alpha in macrophages. Telmisartan induced the mRNA expression of CD36 and ATP-binding cassette transporters A1 and G1 (ABCA1/G1), and these effects were abrogated by PPAR gamma small interfering RNA. Telmisartan, but not other ARBs, inhibited lipopolysaccharide-induced mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha, and these effects were abrogated by PPAR gamma small interfering RNA. Moreover, telmisartan suppressed oxidized low-density lipoprotein-induced macrophage proliferation through PPAR gamma activation. In apolipoprotein E(-/-) mice, telmisartan increased the mRNA expression of ABCA1 and ABCG1, decreased atherosclerotic lesion size, decreased the number of proliferative macrophages in the lesion, and suppressed MCP-1 and tumor necrosis factor-alpha mRNA expression in the aorta. Conclusion-Telmisartan induced ABCA1/ABCG1 expression and suppressed MCP-1 expression and macrophage proliferation by activating PPAR gamma. These effects may induce antiatherogenic effects in hypertensive patients. (Arterioscler Thromb Vasc Biol. 2011;31:1268-1275.)

引用

页码：1268 / U52

页数：14

共 54 条

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