Inhibition of MMP‐2 activation and release as a novel mechanism for HDL‐induced cardioprotection

High density lipoproteins (HDL) protect the heart against ischemia/reperfusion (I/R) injury, and matrix metalloproteinase‐2 (MMP‐2) directly contributes to cardiac contractile dysfunction after I/R. To investigate the possible involvement of MMP‐2 inhibition in HDL‐mediated cardioprotection, isolated rat hearts underwent 20 min of low‐flow ischemia and 30 min of reperfusion. Plasma‐derived and synthetic HDL attenuated the I/R‐induced cardiac MMP‐2 activation and release in a dose‐dependent way. The attenuation of I/R‐induced MMP‐2 activation by HDL correlated with the reduction of post‐ischemic contractile dysfunction and cardiomyocyte necrosis. These results indicate prevention of MMP‐2 activation as a novel mechanism for HDL‐mediated cardioprotection.