Abstract
Background: Acute coronary syndrome is a leading cause of mortality worldwide. Obesity-related disorders are associated with an increased prevalence of cardiovascular disease as well as an increased cardiac damage after acute coronary syndrome. Although C1q/TNF-related protein (CTRP) 9 is an adipocytokine with beneficial properties for glucose metabolism and endothelial function, nothing is known about the role of CTRP9 in ischemic heart disease. Here we investigated the effect of CTRP9 on acute myocardial injury in a mouse model and examined the regulation of adipocyte CTRP9. Methods and Results: Wild-type (WT) mice were subjected to 60 minutes of myocardial ischemia followed by 24 hours of reperfusion. An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was intravenously injected into WT mice 3 days before surgery. Administration of Ad-CTRP9 reduced infarct size and myocyte apoptosis following myocardial ischemia/reperfusion, which was associated with an elevated phosphorylation of AMP-activated protein kinase (AMPK) in ischemic heart. In cultured cardiac myocytes, treatment with CTRP9 protein attenuated apoptosis during hypoxia/reoxygenation and enhanced AMPK signaling. Meanwhile, inhibition of AMPK activity blocked the anti-apoptotic effect of CTRP9. Plasma CTRP9 levels were reduced in diet-induced obese and genetic obese db/db mice. In addition, myocardial ischemia/reperfusion resulted in a significant reduction of circulating CTRP9 levels with decrease in its expression in adipose tissue. After reperfusion, the expression of inflammatory cytokines and NADPH oxidase components was upregulated in adipose tissue, which was accompanied by increased plasma free fatty acid levels. Treatment of adipocytes with palmitic acid or the inducers of inflammation and oxidative stress reduced CTRP9 expression. Furthermore, systemic delivery of CTRP9 protein at the time of reperfusion attenuated myocardial infarct size in response to ischemia/reperfusion. Conclusion: CTRP9 exerts a cardioprotective action during ischemia/reperfusion via AMPK-dependent mechanism. Thus, the enhancement or supplementation of CTRP9 can be novel therapeutic strategies for the treatment of acute coronary syndrome. .
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
