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.
Bellosta
Stefano
S
Department of Pharmacological Sciences, University of Milano, Italy.
Gomaraschi
Monica
M
Canavesi
Monica
M
Rossoni
Giuseppe
G
Monetti
Mara
M
Franceschini
Guido
G
Calabresi
Laura
L
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D018076:DNA, Complementary; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D061965:Matrix Metalloproteinase Inhibitors; D017382:Reactive Oxygen Species; D020778:Matrix Metalloproteinase 2