Cardiomyocyte- specific GPR22 overexpression ameliorates cardiac injury in mice with acute myocardial infarction

The activation of G protein-coupled receptors (GPCR) signaling by external stimuli has been thought to play roles in inducing cardiac stress and stress responses. GPR22 is an orphan GPCR expressed in brains and hearts, while its expression level is associated with cardiovascular damages in diabetes. Previous studies indicated that loss of GPR22 expression increases the susceptibility to heart failure-post ventricular pressure overload, suggesting a protective role of GPR22 in mechanical cardiac stress. However, the participation and underlying signaling of GPR22 in cardiac stress response to ischemic stress remain unknown. In this study, we applied cultured cells and a transgenic mouse model with cardiomyocyte-specific GPR22 overexpression to examine the influence of ischemic stress on GPR22 expression as well as to determine the role of GPR22 in myocardial ischemic injury. To induce acute myocardial infarction (AMI), left coronary artery ligation was performed on eight-week-old male GPR22 transgenic mice, followed by histopathological and biochemical examination four weeks post-induction of AMI. Results showed that GPR22 expressions in H9C2 and RL-14 cells, two cardiomyocyte cell lines, were reduced by cobalt chloride (CoCl 2 ) treatment. Reduced expression of myocardial GPR22 was also observed in mice with acute myocardial infraction (AMI). Histopathological examinations demonstrated the protective role of GPR22 overexpression in ameliorating myocardial infarction in mice with AMI. Furthermore, the myocardial level of Bcl-2 and activation of PI3K-Akt signaling were reduced by ischemic stress and increased by GPR22 over-expression. In conclusion, myocardial ischemic stress reduced the cardiac expression of GPR22, while overexpression of GPR22 in cardiomyocytes upregulated Akt signaling and ameliorated myocardial injury induced by ischemic stress. This research was funded by the Chang Gung Medical Foundation (CMRPG 8K0321) and the National Science and Technology Council, Taiwan (NSC 111-2320-B-182A-005-MY2) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.