Adiponectin ameliorates endotoxin-induced acute cardiac injury.

Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS-) induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10mg/kg) was intraperitoneally injected into wild-type (WT) and adiponectin-knockout (APN-KO) mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV) systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF-alpha and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN) improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF-alpha and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction.