Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice

Ava K. Chow, Edwin E. Daniel, Richard Schulz
2010 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
more » ... 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.
doi:10.1152/ajpheart.01195.2009 pmid:20693397 fatcat:ay4xbqpnmrffjgoa5t6kfzpnze