Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2011 |
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Erschienen: |
2011 |
Enthalten in: |
Zur Gesamtaufnahme - volume:300 |
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Enthalten in: |
American journal of physiology. Heart and circulatory physiology - 300(2011), 4 vom: 07. Apr., Seite H1274-81 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Jasmin, Jean-François [VerfasserIn] |
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Links: |
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Themen: |
Caveolin 1 |
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Anmerkungen: |
Date Completed 20.06.2011 Date Revised 08.04.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1152/ajpheart.01173.2010 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM205634443 |
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100 | 1 | |a Jasmin, Jean-François |e verfasserin |4 aut | |
245 | 1 | 0 | |a Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
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700 | 1 | |a Rengo, Giuseppe |e verfasserin |4 aut | |
700 | 1 | |a Lymperopoulos, Anastasios |e verfasserin |4 aut | |
700 | 1 | |a Gupta, Ratika |e verfasserin |4 aut | |
700 | 1 | |a Eaton, Gregory J |e verfasserin |4 aut | |
700 | 1 | |a Quann, Kevin |e verfasserin |4 aut | |
700 | 1 | |a Gonzales, Donna M |e verfasserin |4 aut | |
700 | 1 | |a Mercier, Isabelle |e verfasserin |4 aut | |
700 | 1 | |a Koch, Walter J |e verfasserin |4 aut | |
700 | 1 | |a Lisanti, Michael P |e verfasserin |4 aut | |
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