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(Circulation. 2007;115:1904-1911.)
© 2007 American Heart Association, Inc.

Molecular Cardiology

Targeted Deletion of Class A Macrophage Scavenger Receptor Increases the Risk of Cardiac Rupture After Experimental Myocardial Infarction

Kenichi Tsujita, MD; Koichi Kaikita, MD; Takanori Hayasaki, MD; Tsuyoshi Honda, MD; Hironori Kobayashi, MD; Naomi Sakashita, MD; Hiroshi Suzuki, PhD; Tatsuhiko Kodama, MD; Hisao Ogawa, MD; Motohiro Takeya, MD

From the Departments of Cell Pathology (K.T., T. Honda, H.K., N.S., M.T.) and Cardiovascular Medicine (K.T., K.K., T. Hayasaki, H.O.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; National Research Center for Protozoan Disease (H.S.), Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan; and Department of Molecular Biology and Medicine (T.K.), Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.

Correspondence to Koichi Kaikita, MD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. E-mail kaikitak{at}kaiju.medic.kumamoto-u.ac.jp

Received June 13, 2006; accepted February 2, 2007.

Background— Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A–deficient (SR-A^–/–) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction.

Methods and Results— Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A^–/– and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A^–/– mice than in WT mice (P=0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A^–/– mice and 12% (6 of 51 mice) in WT mice (P=0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A^–/– mice compared with WT mice. Real-time reverse transcription–polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A^–/– mice compared with WT mice. Furthermore, SR-A^–/– mice showed augmented expression of tumor necrosis factor- and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor- and decreased interleukin-10 expression in activated SR-A^–/– macrophages.

Conclusions— The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor- and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.

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