Year: 2006
Type: article
Abstract: Studies in advanced heart failure (HF) show down-regulation of fatty acid oxidation (FAO) genes, possibly due to decreased expression of the nuclear transcription factors peroxisome proliferator activated receptor α (PPARα) and/or retinoid X receptor α (RXRα).The time course of this down-regulation, however, is unclear.Additionally, myocardial accumulation of lipids is associated with cardiac dysfunction and has been proposed to be a causative factor in the progression of HF.The goal of this dissertation was to test the hypotheses that (i) mRNA and protein levels of PPARα, RXRα and the mRNA and protein expression of PPARα/RXRα regulated FAO enzymes would progressively decrease in HF, and (ii) activation of the fatty acid metabolic pathway with either a direct PPARα agonist or high fat feeding would increase myocardial triglyceride and/or ceramide and exacerbate left ventricular (LV) dysfunction and dilation in established HF.Studies were conducted in the rat infarct model of HF.Rats underwent left coronary artery ligation or sham surgery and 8 weeks later were either untreated, fed a high fat diet (45% kcal from fat), or fed the PPARα agonist fenofibrate (150 mg•kg -1 •day - 1 ).At either 8 or 20 weeks post ligation (12 weeks after initiation of treatment), LV Acetyl-CoA Pyruvate CitricAcid Cycle PDH Lactate Lactate GLYCOLYSIS Glucose CO 2 Fatty Acyl-Carnitine Fatty Acyl-CoA
Author: Eric E. Morgan
Institution: Case Western Reserve University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2475134391