Abstract
Matrix metalloproteinase‐2 (MMP‐2) proteolyzes troponin I (TnI), myosin light chain‐1 (MLC‐1) and α‐actinin within cardiomyocytes in hearts challenged with ischemia and reperfusion (I/R).MMP‐2 is also co‐localized with caveolin‐1 (Cav‐1) in cardiomyocytes. Cav‐1 inhibits MMP‐2 activity. Cav‐1 null (Cav‐1−/−) hearts have increased MMP‐2 activity. How this affects heart function in response to physiological and pharmacological challenges, and whether this has an impact on known MMP‐2 substrates, is unknown.Cav‐1−/− or control (Cav‐1+/+) hearts were isolated and perfused as working hearts. Hearts were perfused aerobically for 30 min followed by both physiological (preload varied between 7‐22.5 mmHg) and pharmacological (0.1‐100 nM isoproterenol) challenges.Cardiac function between the Cav‐1−/− vs Cav‐1+/+ hearts did not differ in either challenge. Gelatin zymography of heart homogenates showed no differences in MMP‐2 activity. Protein levels of MMP‐2, TnI, MLC‐1 and α‐actinin were similar between Cav‐1+/+ and Cav‐1−/− hearts. Hearts briefly perfused for 10 min showed more MMP‐2 activity compared with hearts perfused for 90 min. Prolonged perfusion and the oxidative stress inherent in the isolated working heart procedure may release MMP‐2 from the heart. MMP‐2 proteolysis of intracellular proteins may be dependent upon its activation in I/R.This work is supported by HSF, CIHR and AHFMR.
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