Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction

Jean François Jasmin, Giuseppe Rengo, Anastasios Lymperopoulos, Ratika Gupta, Gregory J. Eaton, Kevin Quann, Donna M. Gonzales, Isabelle Mercier, Walter J. Koch, Michael P. Lisanti

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Caveolin 1
Myocardial Infarction
Knockout Mice
Myocardial Ischemia
Ligation
Brain Ischemia
Wounds and Injuries
Myocardial Ischemic Preconditioning
Hindlimb
Stroke Volume
Adrenergic Agents
Adrenergic Receptors
Genes
Reperfusion
Echocardiography
Coronary Vessels

Keywords

  • β-adrenergic receptors
  • Contractility
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction. / Jasmin, Jean François; Rengo, Giuseppe; Lymperopoulos, Anastasios; Gupta, Ratika; Eaton, Gregory J.; Quann, Kevin; Gonzales, Donna M.; Mercier, Isabelle; Koch, Walter J.; Lisanti, Michael P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 300, No. 4, 04.2011.

Research output: Contribution to journalArticle

Jasmin, Jean François ; Rengo, Giuseppe ; Lymperopoulos, Anastasios ; Gupta, Ratika ; Eaton, Gregory J. ; Quann, Kevin ; Gonzales, Donna M. ; Mercier, Isabelle ; Koch, Walter J. ; Lisanti, Michael P. / Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction. In: American Journal of Physiology - Heart and Circulatory Physiology. 2011 ; Vol. 300, No. 4.
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