Abstract 20282: Increased Circulating Levels of Total and Very Long-Chain Ceramides as Markers of Abnormal Lipid Metabolism and Lipotoxicity in Patients With Chronic Stable Heart Failure
Introduction: Heart failure (HF) is associated with myocardial and systemic metabolic derangements. Ceramides, a class of sphingolipids, have been associated with autophagy and mitochondrial dysfunction in cardiomyocytes and subsequent metabolic aberration in the heart.
Hypothesis: We hypothesized that serum ceramide levels would be higher in patients with stable HF compared to healthy controls.
Methods: All subjects completed a medical history questionnaire and cardiopulmonary exercise test. Serum samples were obtained from all HF patients (NYHA II-III) and control subjects. After lipid extraction, total and individual ceramide species were measured by LC-MS/MS (MS ACQUITY UPLC).
Results: Our study included 31 patients with stable HF (59±2 yrs, LVEF 27.9±1.4, BMI 29±1 kg/m2) and 10 non-HF controls (51±3 yrs, BMI 26±1 kg/m2). Patients with HF showed reduced exercise tolerance compared to controls (Peak VO2 15.3±3.8 vs. 31.3±2.6 ml/min/kg; p<0.001). Total circulating ceramides showed a trend towards higher levels in patients with HF compared to controls (5.5±0.27 vs. 4.5±0.3 uM; p=0.0556). In addition, several individual species of ceramides, in particular, very long-chain ceramides, were significantly increased in HF patients compared to control (C16:1: 0.11±0.01 vs. 0.08±0.01 uM, p<0.05; C20:1: 0.01±0.001 vs. 0.005±0.001 uM, p<0.05; C22:1: 0.07±0.0078 vs. 0.04±0.008, p<0.01; C24:1: 1.3±0.06 vs. 0.77±0.08 uM, p<0.001).
Conclusions: Serum ceramide levels are higher in patients with HF compared to controls with significant differences in individual ceramide species. In particular, very long-chain ceramides (C22 and C24), known to be associated with lipotoxicity and inflammation, were found to be higher in HF. These findings implicate circulating ceramides in the pathogenesis of metabolic abnormalities in HF patients. Circulating ceramides might potentially be useful diagnostic markers of abnormal lipid metabolism and lipotoxicity in patients with HF.
Author Disclosures: L.Y. Deng: None. R. Ji: None. R. Givens: None. D.L. Templeton: None. C. Wu: None. P. Schulze: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.