Abstract 11985: C1q / tnf-Related Protein 9 Protects Against Acute Myocardial Injury
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. Recently, we have reported that CTRP9 prevents adverse vascular remodeling in response to injury. Here, we investigated the effect of CTRP9 on acute cardiac injury with loss-of-function genetic manipulations.
Methods and Results: CTRP9-deficient (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from Wild-type (WT) mice under basal conditions. CTRP9-KO mice showed increased myocardial infarct size and elevated expression of inflammatory cytokines including TNF-α and IL-6 in ischemic heart following ischemia-reperfusion compared with WT mice. CTRP9-KO mice also had exacerbated contractile left ventricle (LV) dysfunction and increased myocardial expression of inflammatory cytokines following intraperitoneal injection of lipopolysaccharide (LPS) compared with WT mice. Conversely, systemic delivery of an adenoviral vector expressing CTRP9 (Ad-CTRP9) attenuated inflammatory responses to myocardial ischemia-reperfusion or LPS administration in WT mice. In cultured cardiac myocytes, treatment with CTRP9 protein suppressed LPS-stimulated expression of TNF-α and IL-6 with an accompanying reduction of NFkB phosphorylation. Treatment of cardiac myocytes with CTRP9 enhanced AMPK phosphorylation, and transduction with dominant-negative mutant form of AMPK reversed the suppressive effect of CTRP9 on TNF-α and IL-6 expression. Furthermore, systemic administration of Ad-CTRP9 improved LPS-induced cardiac dysfunction in WT mice but not in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK.
Conclusions: These findings suggest that CTRP9 protects against acute cardiac damage in response to pathological stimuli by suppressing inflammatory reactions through AMPK-dependent mechanisms.
Author Disclosures: T. Kambara: None. R. Shibata: None. K. Ohashi: None. Y. Joki: None. S. Hayakawa: None. M. Ito: None. D. Yuasa: None. N. Ouchi: None. T. Murohara: None.
- © 2014 by American Heart Association, Inc.