Abstract 390: End-stage Human Heart Failure is Characterized by a Deficit in Energetic Lipids in Both Diabetic and Non-diabetic Patients
Introduction: Animal models and human studies have identified increased intramyocardial lipid accumulation and a lipotoxicity hypothesis has been emerging as a mechanism of myocardial dysfunction in diabetes. We have identified a significant decrease in energetic lipids in chronic advanced non-diabetic heart failure. We hypothesized that intramyocardial lipid species would be increased in diabetic as compared to non-diabetic end-stage heart failure patients.
Methods: Left ventricular samples procured at the time of orthotopic heart transplantation from non-diabetic (IDCM n=8) and diabetic (DCMDM n=8) patients as well as organ donors with (NFDM) and without a history of diabetes (Donor) were quantitated for lipids with high-resolution mass spectrometry . Stable isotope labeled essential nutrient in cell culture internal standards for acyl-CoAs were generated using [13C3 15N1]-pantotheonate in Hepa1c1c7 cells.
Results: The lipidomic signature of end-stage failing myocardium marked by a significant decrease in energetic lipids, a decreased myocardial Succinyl CoA (p-value 0.0079 for failing versus non-failing diabetic subjects) and a decreased ratio of [Succinyl CoA]/[Acetyl Coa] consistent with deficient TCA cycling, is indistinguishable in diabetic and non-diabetic patients (Figure 1).
Discussion: Despite the known bioenergetic deficits in insulin-resistant diabetes, we have not identified any significant differences between diabetic and non-diabetic subjects in the lipidomic signature of end-stae failing myocardium. Future studies are needed with focused metabolomics to elucidate differences in the diabetic phenotype of human heart failure.
Author Disclosures: K.C. Bedi: None. N.W. Snyder: None. A. Javaheri: None. J. Brandimarto: None. C. Mesaaros: None. I.A. Blair: None. K.B. Margulies: None. J.E. Rame: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.