Abstract 874: Targeted Deletion of LOX-1 Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice, Reduces Inflammation and Expression of MMPs
Background: LOX-1, a receptor for ox-LDL, is upregulated during myocardial ischemia-reperfusion (I-R) and may contribute to the inflammatory process. Cultured cell studies suggest that LOX-1 activation also induces the expression of MMPs. In the present study, we examined whether ablation of LOX-1 (LOX-1 KO mice) would ameliorate myocardial I-R injury and modulate inflammation and MMPs expression.
Methods and Results: Anesthetized wild-type (n=10) and LOX-1 KO (n=12) mice were subjected to 60 minutes of coronary artery occlusion followed by 60 minutes of reperfusion. Another group of wild-type and LOX-1 KO mice underwent sham I-R. Following I-R, LOX-1 KO mice exhibited significantly smaller myocardial infarct size (24±4% of area at risk vs. 64±4% in the wild-type mice, P<0.01). Leukocyte accumulation in the infarct and the peri-infarct regions was markedly less in the LOX-1 KO mice compared with the wild-type mice. Expression of MMP-2, -3 and -9 were significantly increased following I-/R in the wild-type mice, but to much less extent in the LOX-1 KO mice (P<0.01 between groups). Interestingly, MMP expression was also less in the sham LOX-1 KO mice as compared with wild-type mice (P<0.05).
Conclusion: These findings demonstrate a key role for LOX-1 activation in myocardial I-R injury. The beneficial effects of LOX-1 deletion may relate to the modulation of MMPs and the inflammatory cascade.