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Grant Abstract

Grant Number: 5R21HL084129-02
PI Name: SPARAGNA
Project Title: Influence of Diet on Mitochondria & Cardiolipin During Heart Failure in SHHF Rats

Abstract: DESCRIPTION: This proposal is a response to the PA for "Nutrition and diet in the causation, prevention, and management of heart failure." A novel strategy to attenuate the development of heart failure (HF) is presented using a high linoleic acid diet in Spontaneously Hypertensive Heart Failure (SHHF) Rats. Linoleic acid is an essential fatty acid and its presence in plasma and diet has recently been shown to reduce the risk of mortality from cardiovascular disease in humans. Linoleic acid also promotes the optimal molecular composition of the phospholipid, cardiolipin (CL), an important mitochondrial phospholipid crucial (in its optimal form) for the function of a large number of enzymes involved in oxidative phosphorylation. Since it has been shown that mitochondria cannot make enough ATP to support their function during HF, maintaining CL in its optimal form allows the mitochondria to produce ATP in the most efficient manner. The experiments proposed herein feed a linoleic acid-rich and -poor diet to SHHF rats and study their CL molecular species profile, their mitochondrial function, as well as a wide range of indicators for heart failure severity. The mechanism of action of linoleic acid will also be investigated through activation of the transcription factors, PPARalpha and PPARgamma. Two models of heart failure in the SHHF rat will be studied, a normal course of HF and a rapid induction of HF, brought about by transaortic banding and high salt. NIH recently declared that lipids are understudied, yet may be even more influential than genes and proteins in the induction of disease due to the way in which they can be so readily altered with diet. Furthermore, a simple modification in the diet that could potentially affect the population in such a dramatic way is worth investigating, and our laboratory is the ideal location since we have an in-house colony of SHHF rats, and have developed a novel technique using mass spectrometry to quantify CL molecular species. RELEVANCE: Heart failure is a disease which has reached epidemic proportions. It is currently the most costly cardiovascular disorder in the US, and unlike other cardiovascular diseases, shows no sign of slowing its rate of increase. This proposal explores a simple, inexpensive way in which to slow or halt the progression of heart failure, a diet rich in linoleic acid, an essential fatty acid possibly deficient in many people, especially those prone to heart failure.

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