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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/H3490    most recent 00310.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Saito, Y. Articles by Kugiyama, K. Search for Related Content PubMed PubMed Citation Articles by Saito, Y. Articles by Kugiyama, K.

Statin reverses reduction of adiponectin receptor expression in infarcted heart and in TNF--treated cardiomyocytes in association with improved glucose uptake

Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

Submitted 13 March 2007 ; accepted in final form 25 September 2007

Statin treatment improves insulin resistance in skeletal muscle. Thus this study assessed whether statin may affect the myocardial expression levels of AdipoR1 and AdipoR2, receptors of adiponectin that enhance insulin sensitivity, and whether statin may improve insulin resistance in cardiomyocytes. Myocardial infarction (MI) was created by the ligation of the left coronary artery in male mice. Expression levels of mRNA and protein levels of AdipoR1 but not of AdipoR2 were significantly decreased in the remote area as well as in the healed infarcted area in the left ventricles 4 wk after MI. Oral administration of pravastatin (50 mg·kg^–1·day^–1 for 4 wk after MI) reversed the decrease in myocardial expression levels of AdipoR1 independently of changes in serum lipid profiles and insulin levels. With the use of cultured cardiomyocytes, incubation with tumor necrosis factor (TNF)-, a mediator of postinfarction myocardial dysfunction, inhibited AdipoR1 mRNA and protein expression levels. Coincubation of the cells with pravastatin reversed the inhibitory effects of TNF- on AdipoR1 expression. In parallel, pravastatin reversed the TNF--induced decrease in globular adiponectin-induced 2-deoxy-D-[³H]glucose uptake in insulin-treated cultured cells. Moreover, this effect of pravastatin was inhibited by the suppression of AdipoR1 expression by small-interfering RNA specific for AdipoR1. Incubation with H₂O₂ reduced AdipoR1 expression in cultured cardiomyocytes that were attenuated by N-acetyl-L-cysteine or pravastatin. Pravastatin suppressed TNF--induced intracellular oxidants in cultured cardiomyocytes. In conclusion, pravastatin reversed the reduction of AdipoR1 expression in postinfarction mouse myocardium and in TNF--treated cardiomyocytes partly through an antioxidative mechanism in association with improved glucose uptake.

insulin resistance; myocardial infarction; antioxidant