Myocardial hypertrophy is an adaptive response to a pressure or volume load. However, patients with ventricular hypertrophy are at increased risk for congestive heart failure, sudden death, and myocardial infarction. The metabolic response of cardiac myocytes to an increased load is known to include activation of several fetal pathways that allow the heart to more efficiently utilize glucose and enhance adenosine triphosphate (ATP) production. We have shown that fetal and neonatal myocardium optimizes ATP production from glucose oxidation through activation of the malate/aspartate (mar/asp) and a-glycerophosphate (a-GP) shuttles. The molecular basis of these and other metabolic adaptations in hypertrophied myocardium are just beginning to be explored.
The specific aims of this proposal are to determine if the mal/asp and a- GP shuttles are up-regulated in hypertrophied myocardium, sequence and characterize the aspartate/glutamate carrier (AGC), identify the role of the AGC in regulating mal/asp shuttle flux, and broadly explore molecular regulation of metabolism in hypertrophied myocardium using cDNA microarray techniques. These studies will continue the research career development along a path I have been following for the last decade or more. My commitment to research preceded my postgraduate education and continued through my pediatric cardiology fellowship and postdoctoral training at the NIH. I have been an independent investigator at the University of Iowa for the past six years focusing on studies of the metabolic adaptation of the heart in response to disease and normal development. The research environment at the University of Iowa nurtures young scientists by providing excellent facilities and encouraging collaborations among investigators. It is through collaboration with other investigators that I have learned techniques to expand the questions that can be answered and that has allowed my research career to develop. Unfortunately, focused research time continues to decline as clinical demands increase. Receiving the Independent Scientist Award (K02) would remove most of these clinical duties and allow more concentrated time directed at studying the metabolic development of the heart. This will aid in my long-term goals of increased understanding of the metabolic development of the heart and serving as a role model and guide for clinician-scientists in training.
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