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-α and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-α 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-α and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.
Unimpaired autoreactive T-cell traffic within the central nervous system during tumor necrosis factor receptor-mediated inhibition of experimental autoimmune encephalomyelitis.
