Abstract 4012: Characterization of Adiponectin as an Anti-inflammatory Protein in Patients With Chronic Inflammatory Cardiomyopathy
Background: Adiponectin (APN) is an adipocytokine present in the circulation exerting immunomodulatory, anti-apoptotic and pro-angiogenic effects. APN has recently been shown to prevent remodeling after cardiac injury and to afford protection from viral heart disease. However, the expression of the cytokine and its isoforms as well as its effects has not been studied in inflammatory cardiomyopathy (DCMi).
Materials and Methods: The expression of APN as well as disease outcome in patients with DCMi and in a mouse model of autoimmune myocarditis were studied. Mechanisms of the observed effects were determined in vitro.
Results: APN concentrations (total, high, low molecular weight APN) were significantly higher in patients with DCMi (n=173) when compared with controls (n=30), i.e. 6.81±3.87 μg/mL vs 4.76±2.46 μg/mL for total APN (p<0.05) and did significantly correlate with the amount of cardiac mononuclear infiltrates (CD3+: r=0.158, p<0.05, CD45R0+: r=0.193, p<0.05) as well as systemic inflammation (IL-8 serum levels, r=0.387, p<0.05). Elevated adiponectin concentrations in patients with DCMi significantly correlated with LV-EF (r=−0.376, p<0.001), LVEDD (r=0.207, p<0.05), mean PAP (r=0.378, p<0.05), PCPW (r=0.335, p<0.05) and HI (r=−0.458, p<0.001). At 6 months follow-up, DCMi patients in the upper tertile of adiponectin basal levels showed significantly increased LVEF and decreased LVEDD, that was accompanied by reduced inflammatory infiltrates in cardiac tissue (CD3+, CD45R0+, p<0.05). In accordance with those data, mice with autoimmune myocarditis exhibited elevated plasma APN levels (p<0.01). Gene transfer of APN led to significant downregulation of key regulators of the immune response (i.e. IFNγ, TNFá, IL-17a). In vitro, APN exerted anti-inflammatory effects by significantly ameliorating antigen specific T-cell stimulation (p<0.01), TNFá-mediated NFê B activation (p<0.01), and production of reactive oxygen species in cardiomyocytes commonly observed in inflammatory states.
Conclusion: Our results implicate APN as an anti-inflammatory cytokine that is upregulated during cardiac inflammation inhibiting the chronic inflammatory process in DCMi. High serum concentrations of APN ameliorate the progression of DCMi.