Abstract 16040: Corin Reduces Myocardial Infarction and Protects Against Cardiomyocyte Apoptosis
Corin is a cardiac-selective membrane protease that activates pro-ANP and pro-BNP. Emerging evidence suggests that corin may be a key biomarker and modulator of heart failure in dilated cardiomyopathy, but there is little known about the role of corin in myocardial infarction (MI). In acute MI in mice, we found that corin transcript and protein levels were significantly decreased when compared to non-MI controls 24 hrs post MI (1.0±0.1 vs 0.6±0.1, p=0.01; 1.0±0.04 vs 0.5±0.1, p<0.01). To examine the functional role of corin, we studied effect of transgenic overexpression of corin (corin-Tg) on cardiomyocyte survival in acute MI and we explored the effects of corin on cardiomyocyte survival in vitro. Compared to control, wild-type mice, there was a significant decrease in infarct size in corin-Tg mice (infarct area:left ventricle area, 44±3 % vs 25±3%, p=0.01) and in the ratio of infarct area:area at risk (102±8% vs 63±4%, p<0.001) 24 hrs post MI. Apoptosis was also significantly reduced in the infarcted left ventricle of corin-Tg mice vs. control (TUNEL-positive cells/myocardium mm2, 261±13 vs 106±16, p<0.0001). In the HL-1 mouse cardiomyocyte cell line, overexpression of corin protected HL-1 cells from staurosporine -induced apoptosis by blocking cytochrome c release and caspase 3 cleavage; whereas siRNA knock down of corin in HL-1 cells promoted caspase 3 activation, as evaluated by immunofluorescence staining and Western-blotting. We conclude that experimental myocardial infarction is associated with marked reductions of corin transcript and protein levels in the heart. Overexpression of corin significantly reduces infarct size and protects against cardiomyocyte apoptosis, both in vivo and in vitro. Taken together these data suggest that corin promotes cardiomyocyte survival after MI. Corin appears to mediate its protective role in part by blocking the cytochrome c-caspase 3 mediated apoptotic pathway.
Author Disclosures: D. Wang: Research Grant; Significant; AHA GRANT 14SDG20510068-WANG. R.D. Sullivan: None. I.P. Gladysheva: Research Grant; Significant; NIH RO1. A. Houng: None. R. Tripathi: None. T.M. Fan: None. G.L. Reed: Research Grant; Significant; NIH RO1 grant.
- © 2015 by American Heart Association, Inc.