Abstract 10923: C1q/Tnf Related Protein9 Prevents Lps Induced Acute Cardiac Injury Through An Ampk Dependent Mechanism
Background: Obesity-related disorders are associated with an increased risk for cardiovascular disease. C1q/TNF-related protein (CTRP) 9 is an anti-diabetic adipokine that is downregulated in obese mice. CTRP9 exerts beneficial effects on glucose metabolism and vascular function. We have reported that CTRP9 exerts beneficial effects on ischemic myocardial damage and vascular injury. Here, we investigated the effect of CTRP9 on lipopolysaccharide-induced acute cardiac injury in vivo and assessed its mechanisms.
Methods and Results: LPS (10mg/kg) was intraperitoneally injected into the abdomen of wild-type (WT) mice. Adenoviral vectors expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control were intravenously injected into WT mice 3 days prior to the LPS injection. Systemic administration of Ad-CTRP9 to WT mice led to a 3.3-fold increase in circulating CTRP9 levels and improvement of LPS-induced contractile dysfunction in the heart. Ad-CTRP9 also reduced LPS-stimulated expressions of pro-inflammatory cytokines such as TNF-α and IL-6 in the heart. In cultured cardiac myocytes, treatment with CTRP9 protein suppressed LPS-induced expressions of TNF-α and IL-6. Treatment of cardiac myocytes with CTRP9 enhanced the phosphorylation of AMPK. Inhibition of AMPK activity by transduction with dominant-negative mutant forms of AMPK reversed the suppressive effect of CTRP9 on TNF-α and IL-6 expressions. Furthermore, Ad-CTRP9 treatment had no effects on the LPS-induced cardiac dysfunction in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK.
Conclusion: CTRP9 ameliorates endotoxin-induced myocardial dysfunction and inflammation through AMPK-dependent mechanisms, suggesting that CTRP9 represents a therapeutic target for the treatment of acute cardiac injury.
- © 2013 by American Heart Association, Inc.