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Grant Abstract

Grant Number: 1R21HL091307-01A1
PI Name: STANLEY
Project Title: Omega-3 Fatty Acids and Heart Failure

Abstract: DESCRIPTION (provided by applicant): Despite aggressive diagnosis and treatment, hypertension remains a major clinical problem and frequently leads to chronic heart failure (HF) The omega-3 fatty acids found in fish oils (eicosapentanoic acid (EPA) and docohexanoic acid (DHA)) and in some plants (1-linolenic acid (ALA) in flax seed or canola oil) may prevent the development of left ventricular (LV) hypertrophy and HF in hypertension. We recently observed that the addition of fish oil (2.8% of energy consumption as EPA+DHA) to the diet of rats subjected to hypertension attenuated LV hypertrophy and prevented the development of LV dysfunction. HF causes down-regulation of peroxisome proliferator activated receptor (PPAR)-regulated genes (which control expression of proteins involved in energy metabolism) and decreases fatty acid metabolism and impairs mitochondrial function. Omega-3 fatty acids are potent ligands for PPARs, and thus could activate cardiac gene expression and improve mitochondrial metabolism and cardiac function. Fish oil intake also increased the cardioprotective hormone adiponectin in plasma, which we found correlated with prevention of cardiac dysfunction in pressure overloaded rats. The goal of this application is to understand how omega-3 fatty acids affect the development and progression of HF in pressure-overload hypertension. Studies will be performed in vivo using well established aortic banding models of LV hypertrophy and HF. Our primary hypothesis is that omega 3FA (either from fish oil or ALA) will attenuate LVH and prevent HF due to increased expression of PPAR-regulated genes and increased serum adiponectin concentration. The two Specific Aims are: 1)Determine the effects of dietary omega 3FA (from either fish oil (EPA+DHA) or flax seed oil (ALA)) on the development of HF during hypertension induced by chronic aortic banding in rats. In addition, the ability of omega 3FA to reverse established HF will be assessed. 2) Determine if increased adiponectin is essential for the prevention of LVH and HF observed with omega 3FA supplementation. WT and adiponectin knock out mice will be subjected to aortic banding and fed either normal chow or chow supplemented with I-3FAs from fish oil. Echocardiography and LV pressure-volume measurements will be used to assess development of hypertrophy and HF, and alterations in gene expression and metabolic enzymes will be measured. PUBLIC HEALTH RELEVANCE Despite aggressive diagnosis and treatment, hypertension remains a major clinical problem and frequently leads to chronic heart failure. The omega-3 fatty acids found in fish oils and in some plants may prevent the development heart failure. The goal of this application is to understand how omega-3 fatty acids affect the development and progression of HF in hypertension.

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