Abstract 1437: Target Deletion of Class A Macrophage Scavenger Receptor Contributes to Susceptibility of Cardiac Rupture After Experimental Myocardial Infarction in Mice
Background Cardiac rupture remains a serious complication of acute myocardial infarction (MI), and has been shown to be caused by disruption of extracellular matrix (ECM) structures, which is triggered by early inflammation in response to ischemic damage. Recent studies demonstrated that the class A macrophage scavenger receptor (SR-A) could bind to a broad range of ligands resulting in a wide range activity including modulation of the inflammatory response. This study was conducted to evaluate the relationship between SR-A and left ventricular healing after MI by using SR-A gene deficient (SR-A−/−) mice.
Methods and Results Experimental MI was produced by ligating the left coronary artery in SR-A−/− and wild type (WT) male mice. We examined cardiac rupture rate, survival rate, echocardiography, ECM degradation, and expression of inflammatory cytokines at the infarcted and noninfarcted regions after MI in both groups of mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A−/− mice than in WT mice (Log-rank, P=0.03). Importantly, the death due to cardiac rupture within 1 week after MI was 31% (17/54) of SR-A−/− mice and 12% (6/51) of WT mice (P=0.01). There was no significant difference in the infiltration of inflammatory cells into the infarcted myocardium between the 2 groups. In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A−/− mice compared to WT mice at 3 days after MI. Real-time RT-PCR showed that the expression of matrix metalloproteinase (MMP)-9 mRNA increased significantly in the infarcted myocardium in SR-A−/− mice compared to WT mice at 3 days after MI. Furthermore, SR-A deficient-mice showed augmented expression of the proinflammatory cytokine, TNF-α, and reduction of the antiinflammatory cytokine, IL-10, in the infarcted myocardium at 3 days after MI. In vitro experiments also demonstrated increased TNF-α and decreased IL-10 expression in acetyl-LDL-activated SR-A−/− macrophages.
Conclusions These findings suggested that SR-A deficiency might cause impairment of wound healing resulting in cardiac rupture via insufficient production of IL-10 and enhanced expression of TNF-α and MMP. SR-A might contribute to the prevention of cardiac rupture after MI.