Abstract：
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.
摘要：
GLP-1R激动剂改善缺血性心脏病预后.在这里，我们研究了GLP-1R依赖性的心室损伤的适应性和心脏保护反应。Glp1r（-/-）心脏在基因表达方面表现出特定的差异，但心肌梗死（MI）或实验性阿霉素诱发的心肌病后的死亡率和左心室（LV）重塑正常。在Glp1r(CM-/-)小鼠中心肌细胞GLP-1R的选择性破坏在LAD冠状动脉闭塞后的存活或LV重塑中没有产生差异。出乎意料的是,GLP-1R激动剂利拉鲁肽在LAD冠状动脉闭塞后的Glp1r(CM-/-)小鼠中仍能产生强大的心脏保护作用,并提高存活率.尽管利拉鲁肽增加了Glp1r（CM-/-）小鼠的心率（HR），Glp1r（CM-/-）小鼠的基础HR显着降低。因此，内源性心肌细胞GLP-1R活性不是对缺血性或心肌病性损伤的适应性反应所必需的，并且对于GLP-1R激动剂诱导的心脏保护或增强的变时活性是可有可无的。然而,心肌细胞GLP-1R对于控制小鼠的HR是必需的。
