Fatty acid oxidation enzyme gene expression is downregulated in the failing heart.

Abstract:

BACKGROUND:During the development of heart failure (HF), the chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac energy substrate preferences, is thought to maintain aerobic energetic balance. The regulatory mechanisms involved in this metabolic response are unknown. METHODS AND RESULTS:To characterize the expression of genes involved in mitochondrial fatty acid beta-oxidation (FAO) in the failing heart, levels of mRNA encoding enzymes that catalyze the first and third steps of the FAO cycle were delineated in the left ventricles (LVs) of human cardiac transplant recipients. FAO enzyme and mRNA levels were coordinately downregulated (> 40%) in failing human LVs compared with controls. The temporal pattern of this alteration in FAO enzyme gene expression was characterized in a rat model of progressive LV hypertrophy (LVH) and HF [SHHF/Mcc-facp (SHHF) rat]. FAO enzyme mRNA levels were coordinately downregulated (> 70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and steady-state levels of medium-chain acyl-CoA dehydrogenase, which catalyzes a rate-limiting step in FAO, were not significantly reduced until the HF stage, indicating additional control at the translational or post-translational levels in the hypertrophied but nonfailing ventricle. CONCLUSIONS:These findings identify a gene regulatory pathway involved in the control of cardiac energy production during the development of HF.

journal_name

Circulation

journal_title

Circulation

authors

Sack MN,Rader TA,Park S,Bastin J,McCune SA,Kelly DP

doi

10.1161/01.cir.94.11.2837

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

2837-42

issue

11

eissn

0009-7322

issn

1524-4539

journal_volume

94

pub_type

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