title: Telmisartan exerts antiatherosclerotic effects by activating peroxisome proliferator-activated receptor-γ in macrophages.
abstract: 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.
  
  
  RESULTS
  In macrophages, telmisartan increased peroxisome proliferator-activated receptor-γ (PPARγ) activity and PPAR ligand-binding activity. In contrast, 3 other ARBs, losartan, valsartan, and olmesartan, did not affect PPARγ activity. Interestingly, high doses of telmisartan activated PPARα 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 PPARγ small interfering RNA. Telmisartan, but not other ARBs, inhibited lipopolysaccharide-induced mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α, and these effects were abrogated by PPARγ small interfering RNA. Moreover, telmisartan suppressed oxidized low-density lipoprotein-induced macrophage proliferation through PPARγ 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-α mRNA expression in the aorta.
  
  
  CONCLUSIONS
  Telmisartan induced ABCA1/ABCG1 expression and suppressed MCP-1 expression and macrophage proliferation by activating PPARγ. These effects may induce antiatherogenic effects in hypertensive patients.
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. takeshim@gpo.kumamoto-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Norio
authors.initials: N
authors.lastname: Ishii
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukuda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senokuchi
authors.forename: Kayo
authors.initials: K
authors.lastname: Taketa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishimaki-Mogami
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000188:drug therapy*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000187:drug effects*; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D001562:Benzimidazoles; D001565:Benzoates; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D000077333:Telmisartan