Abstract 20507: Increased Adipocytokine Signaling in Patients with Advanced Heart Failure Corrects after Mechanical Unloading through Ventricular Assist Device Implantation
Heart failure (HF) is a clinical syndrome associated with metabolic abnormalities marked by inflammation, insulin resistance (IR) and changes in serum levels of the adipocytokines leptin, adiponectin and resistin. We hypothesized that hemodynamic correction through implantation of a ventricular assist device (VAD) reverses adipocyte activation and corrects adipocytokine levels in HF. Serum was collected from 42 patients with advanced HF before and after VAD implantation and 8 controls. Adipocytokine expression was assessed in adipose tissue and receptors in muscle and myocardium. Serum levels of insulin, leptin, adiponectin and resistin were measured by ELISA and IR calculated using HOMA-IR. Clinical data were obtained from medical records. The study population had a mean age of 52±2.6 yrs, ejection fraction of 18±1% and VAD duration of 117±13 days. VAD implantation reduced HbA1c (7.7±0.78 to 6.2±0.4 %, p<0.05) and IR (4.5±0.56 to 3.2±0.45, p<0.05). Serum triglycerides, HDL, LDL and cholesterol increased after VAD (p<0.05). Serum adiponectin (6.5±2.3 ug/ml in con vs 12.8±8.9 ug/ml in HF; p=0.07) and resistin (0.8±0.2 ng/ml in con vs 137.7±38.8 ng/ml in HF; p<0.05) increased in HF compared to controls while leptin decreased in HF (10.9±4.6 ng/ml in con vs 4.9±1.6 ng/ml in HF, p=0.14). Notably, IR correlated with serum resistin (r2 = 0.33; p<0.05). After VAD implantation, reduced serum levels of adiponectin (7.2±4.1 ug/ml, p<0.05) and resistin (91.8±25.4 ng/ml, p=0.09) without changes in leptin were found. Adiponectin expression in fat decreased after VAD implantation (−65%; p<0.03) without significant changes in leptin and resistin expression. Reduced myocardial expression of adiponectin receptors AdipoR1 (−77%; p<0.05) and AdipoR2 (−60%) and leptin receptor (−50%) was found after VAD implantation. In muscle, expression of AdipoR1 and AdipoR2 also decreased (−54%) while leptin receptor expression increased 10-fold (p=0.07). In conclusion, our data demonstrate a distinct activation of adipocytokine signaling in patients with HF and the reversibility of these changes after hemodynamic correction through VAD implantation. These findings suggest an active role of adipose tissue in the pathogenesis of metabolic derangements in advanced HF.
- © 2010 by American Heart Association, Inc.