PMID- 21474824
OWN - NLM
STAT- MEDLINE
DCOM- 20110726
LR  - 20181201
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 31
IP  - 6
DP  - 2011 Jun
TI  - Telmisartan exerts antiatherosclerotic effects by activating peroxisome 
      proliferator-activated receptor-gamma in macrophages.
PG  - 1268-75
LID - 10.1161/ATVBAHA.110.222067 [doi]
AB  - 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 (PPARgamma) activity and PPAR 
      ligand-binding activity. In contrast, 3 other ARBs, losartan, valsartan, and 
      olmesartan, did not affect PPARgamma activity. Interestingly, high doses of 
      telmisartan activated PPARalpha 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 PPARgamma 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 PPARgamma small interfering RNA. Moreover, telmisartan suppressed 
      oxidized low-density lipoprotein-induced macrophage proliferation through PPARgamma 
      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 PPARgamma. These effects may induce antiatherogenic 
      effects in hypertensive patients.
FAU - Matsumura, Takeshi
AU  - Matsumura T
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan. takeshim@gpo.kumamoto-u.ac.jp
FAU - Kinoshita, Hiroyuki
AU  - Kinoshita H
FAU - Ishii, Norio
AU  - Ishii N
FAU - Fukuda, Kazuki
AU  - Fukuda K
FAU - Motoshima, Hiroyuki
AU  - Motoshima H
FAU - Senokuchi, Takafumi
AU  - Senokuchi T
FAU - Taketa, Kayo
AU  - Taketa K
FAU - Kawasaki, Shuji
AU  - Kawasaki S
FAU - Nishimaki-Mogami, Tomoko
AU  - Nishimaki-Mogami T
FAU - Kawada, Teruo
AU  - Kawada T
FAU - Nishikawa, Takeshi
AU  - Nishikawa T
FAU - Araki, Eiichi
AU  - Araki E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110407
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (PPAR gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (oxidized low density lipoprotein)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Animals
MH  - Apolipoproteins E/physiology
MH  - Atherosclerosis/*drug therapy
MH  - Benzimidazoles/*pharmacology
MH  - Benzoates/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Gene Expression Regulation/drug effects
MH  - Lipoproteins, LDL/antagonists & inhibitors
MH  - Macrophages/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - PPAR gamma/*drug effects
MH  - Telmisartan
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2011/04/09 06:00
MHDA- 2011/07/27 06:00
CRDT- 2011/04/09 06:00
PHST- 2011/04/09 06:00 [entrez]
PHST- 2011/04/09 06:00 [pubmed]
PHST- 2011/07/27 06:00 [medline]
AID - ATVBAHA.110.222067 [pii]
AID - 10.1161/ATVBAHA.110.222067 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2011 Jun;31(6):1268-75. doi: 
      10.1161/ATVBAHA.110.222067. Epub 2011 Apr 7.