title: Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction.
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.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. jeanfrancois.jasmin@jefferson.edu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.forename: Anastasios
authors.initials: A
authors.lastname: Lymperopoulos
authors.forename: Ratika
authors.initials: R
authors.lastname: Gupta
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Eaton
authors.forename: Kevin
authors.initials: K
authors.lastname: Quann
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gonzales
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mercier
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D013318:Stroke Volume / Q000502:physiology; D014463:Ultrasonography
chemical_list: D051242:Caveolin 1; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases