Liraglutide produced robust cardioprotection and increased survival in mice lacking cardiomyocyte GLP-1R following LAD coronary artery occlusion.
Does liraglutide improve survival and LV remodeling in cardiomyocyte-specific GLP-1R knockout mice following ventricular injury?
Cardiomyocyte GLP-1R is essential for basal heart rate control but is not required for the cardioprotective and survival benefits of GLP-1R agonists like liraglutide following ischemic injury.
GLP-1R agonists improve outcomes in ischemic heart disease. Here we studied GLP-1R-dependent adaptive and cardioprotective responses to ventricular injury. Glp1r (-/-) hearts exhibited chamber-specific differences in gene expression, but normal mortality and left ventricular (LV) remodeling after myocardial infarction (MI) or experimental doxorubicin-induced cardiomyopathy. Selective disruption of the cardiomyocyte GLP-1R in Glp1r (CM-/-) mice produced no differences in survival or LV remodeling following LAD coronary artery occlusion. Unexpectedly, the GLP-1R agonist liraglutide still produced robust cardioprotection and increased survival in Glp1r (CM-/-) mice following LAD coronary artery occlusion. Although liraglutide increased heart rate (HR) in Glp1r (CM-/-) mice, basal HR was significantly lower in Glp1r (CM-/-) mice. Hence, endogenous cardiomyocyte GLP-1R activity is not required for adaptive responses to ischemic or cardiomyopathic injury, and is dispensable for GLP-1R agonist-induced cardioprotection or enhanced chronotropic activity. However the cardiomyocyte GLP-1R is essential for the control of HR in mice.
Ussher et al. (Thu,) conducted a other in Myocardial infarction and doxorubicin-induced cardiomyopathy. Liraglutide was evaluated on Survival and left ventricular remodeling. Liraglutide produced robust cardioprotection and increased survival in mice lacking cardiomyocyte GLP-1R following LAD coronary artery occlusion.
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