Journal article
Abstract 390: End-stage Human Heart Failure is Characterized by a Deficit in Energetic Lipids in Both Diabetic and Non-diabetic Patients
Circulation research, v 117(suppl_1)
17 Jul 2015
Abstract
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 [
13
C
3
15
N
1
]-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.
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Details
- Title
- Abstract 390: End-stage Human Heart Failure is Characterized by a Deficit in Energetic Lipids in Both Diabetic and Non-diabetic Patients
- Creators
- Kenneth C Bedi - University of Pennsylvania, Philadelphia PA.Nathaniel W Snyder - Drexel UniversityAli Javaheri - University of Pennsylvania, Philadelphia PA.Jeffery Brandimarto - University of Pennsylvania, Philadelphia PA.Clementina Mesaaros - University of Pennsylvania, Philadelphia PA.Ian A Blair - University of Pennsylvania, Philadelphia PA.Kenneth B Margulies - University of Pennsylvania, Philadelphia PA.J. E Rame - University of Pennsylvania, Philadelphia PA.
- Publication Details
- Circulation research, v 117(suppl_1)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Other Identifier
- 991019170595804721