| Summary: | MSc (Med), School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 2009 === Excess adiposity may increase the risk of heart failure through interactions with conventional risk factors. As cardiomyocyte apoptosis may be an important mechanism responsible for the development of heart failure the aim of the present study was to determine whether obesity enhances a) the increased cardiomyocyte apoptosis that accompanies pressure-overload hypertrophy and b) sympathetic-induced cardiomyocyte apoptosis. The impact of dietary-induced obesity on cardiomyocyte apoptosis was studied in elderly spontaneously hypertensive rats (SHR) and age-matched (8-9 months of age at the beginning of the study) Wistar Kyoto rats (WKY) after a 5 month feeding period and in young WKY rats (1 month of age at the beginning of the study) receiving either isoproterenol (ISO) or the vehicle (saline) for 5 days at the end of the feeding period. To induce obesity rats were fed a diet that promotes hyperphagia. At the end of the feeding period echocardiography was performed. Cardiac myocyte apoptosis was assessed using a TUNEL staining technique. Rats receiving the obesity-inducing diet had increases in body weight and visceral fat content. No further changes in systolic blood pressure were observed in rats during the feeding period. SHRs on the obesity-inducing diet had an increased left ventricular end-diastolic diameter and a decreased endocardial fractional shortening. As compared to lean rats, dietary-induced obesity resulted in an increase in the percentage of cardiomyocytes that were apoptotic in SHRs (3.4±0.5%, p<0.005 vs all other groups) and in WKYs receiving ISO (0.35±0.05%, p<0.05 vs Control-ISO and p<0.01 vs Control-saline and Diet-saline groups). In conclusion, obesity was associated with cardiomyocyte apoptosis through an interaction with pressure-overload hypertrophy
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and excessive sympathetic activation. These findings provide insights into the potential mechanisms through which obesity may promote the development of heart failure.
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