Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice
American Journal of Physiology. Heart and Circulatory Physiology
Chow AK, Daniel EE, Schulz R. Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice. Matrix metalloproteinases (MMPs) are known to degrade components of the extracellular matrix. More recently, in myocardial oxidative stress injury including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and ␣-actinin. MMP activity is regulated at several levels. We recently showed that MMP-2 is localized in the caveolae of cardiomyocytes and
... ardiomyocytes and is negatively regulated by caveolin-1 (Cav-1). The caveolin scaffolding domain of Cav-1 inhibits MMP-2 proteolytic activity in vitro, and Cav-1 Ϫ/Ϫ mouse hearts have increased MMP-2 activity compared with controls. Whether this increase in MMP-2 activity translates to impaired cardiac function is unknown. Hearts isolated from Cav-1 Ϫ/Ϫ mice and their wild-type controls were perfused as isolated working hearts and physiologically challenged with increasing increments of left atrial preload (7-22.5 mmHg). The hearts were then pharmacologically challenged with increasing concentrations of isoproterenol (0.1-100 nM). Functionally, the Cav-1 Ϫ/Ϫ hearts were similar to the controls in heart rate, peak systolic pressure, developed pressure, and rate pressure product. At higher preload pressures, the Cav-1 Ϫ/Ϫ hearts outperformed the control hearts. Coronary flow was significantly higher in Cav-1 Ϫ/Ϫ hearts under all conditions. The highest concentration of isoproternol increased the heart rate of Cav-1 Ϫ/Ϫ hearts more than in controls. Western blot analysis revealed no significant changes in troponin I or ␣-actinin between Cav-1 Ϫ/Ϫ hearts and their controls. There was a significant loss of MMP-2 from both knockout and control hearts during the perfusion. In summary, despite the loss of Cav-1, Cav-1 Ϫ/Ϫ hearts show similar or better cardiac function compared with wild-type hearts following physiological challenge or ␤-adrenergic stimulation in vitro, and this appears unrelated to changes in MMP-2.