Metabolic aspects of neonatal rat cardiomyocyte hypertrophy

Abstract

The consensus view is that cardiac hypertrophy is an adaptive response to increased work caused by a variety of stimuli. While hypertrophy can be defined as an increase in cell mass without an increase in cell number, not all increases are equivalent in type and amount of protein accumulated. Our goal in this study was to identify the common steps in the process of cardiac hypertrophy. Our working hypothesis was that in all forms of cardiac hypertrophy glucose utilization increases and that the percentage of energy derived from fatty-acid oxidation decreases. The first part of this study entailed the development and characterization of a neonatal rat heart cell model. The model had to provide uniform culture conditions for rapid development of hypertrophy by agents acting at different sites in the cardiomyocytes. The second part of this study was composed of an assessment of hypertrophy caused by four pharmacologically distinct agents: norepinephrine, angiotensin-II, endothelin-I and tetradecylglycidic acid. In this part we compared the quantity of protein accumulation and quality of hypertrophy cause by each agent. This task was accomplished by examining the effect of each agent on selected mRNA messages and alteration in DNA content of cardiomyocytes. Here we also examined the effect of protein kinase-C, endothelin-I and angiotensin-II inhibitors on hypertrophy caused by each agent. In the final part of this study, metabolic alteration in hypertrophy caused by each agent was assessed for a potential common pathway to hypertrophy. As part of this analysis, we examined changes in glucose and palmitate oxidation, glucose uptake and role of pentose pathway in hypertrophy resulting from treatment of cardiomyocyte by each agent.