Caveolin-1 Deficiency Exacerbates Cardiac Dysfunction and Reduces Survival in Mice With Myocardial Infarction

Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1274-81. doi: 10.1152/ajpheart.01173.2010. Epub 2011 Feb 4.

Abstract

Caveolin (Cav)-1 has been involved in the pathogenesis of ischemic injuries. For instance, modulations of Cav-1 expression have been reported in animal models of myocardial infarction and cerebral ischemia-reperfusion. Furthermore, ablation of the Cav-1 gene in mice has been shown to increase the extent of ischemic injury in models of cerebral and hindlimb ischemia. Cav-1 has also been suggested to play a role in myocardial ischemic preconditioning. However, the role of Cav-1 in myocardial ischemia (MI)-induced cardiac dysfunction still remains to be determined. We determined the outcome of a permanent left anterior descending coronary artery (LAD) ligation in Cav-1 knockout (KO) mice. Wild-type (WT) and Cav-1 KO mice were subjected to permanent LAD ligation for 24 h. The progression of ischemic injury was monitored by echocardiography, hemodynamic measurements, 2,3,5-triphenyltetrazolium chloride staining, β-binding analysis, cAMP level measurements, and Western blot analyses. Cav-1 KO mice subjected to LAD ligation display reduced survival compared with WT mice. Despite similar infarct sizes, Cav-1 KO mice subjected to MI showed reduced left ventricular (LV) ejection fraction and fractional shortening as well as increased LV end-diastolic pressures compared with their WT counterparts. Mechanistically, Cav-1 KO mice subjected to MI exhibit reduced β-adrenergic receptor density at the plasma membrane as well as decreased cAMP levels and PKA phosphorylation. In conclusion, ablation of the Cav-1 gene exacerbates cardiac dysfunction and reduces survival in mice subjected to MI. Mechanistically, Cav-1 KO mice subjected to LAD ligation display abnormalities in β-adrenergic signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolin 1 / deficiency*
  • Caveolin 1 / genetics
  • Caveolin 1 / physiology
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / physiopathology
  • Cyclic AMP / biosynthesis
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Myocardial Infarction / complications
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / mortality*
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / physiopathology
  • Phosphorylation
  • Receptors, Adrenergic, beta / biosynthesis
  • Stroke Volume / physiology
  • Ultrasonography

Substances

  • Caveolin 1
  • Receptors, Adrenergic, beta
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases