Genetic insights into cardiovascular function and disease

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

We are focusing on a novel pathway that regulates mitochondrial function and cardiovascular exercise capacity that may have implications for tumorigenesis. We have recently shown that the tumor suppressor gene p53 balances the energy generated by respiration and glycolysis and that this effect is primarily mediated through a p53 transcriptional target gene involved in cytochrome c oxidase complex assembly. Mice deficient in p53 display profound deficiencies in aerobic exercise capacity revealing a new function for a well-studied gene mainly associated with cell cycle and genomic regulation. This finding offers possible molecular explanations for some of our previous observations of p53 dependent oxidant generation and heart failure by chemotherapeutic agents and raises new questions. We are further characterizing our preliminary findings, and we are initiating human studies to translate some of these basic observations.[unreadable] [unreadable] Our laboratory is also examining easily accessible human cells important for atherosclerosis to gain new insights into this cardiovascular disease. Using unbiased approaches, we have identified monocyte and macrophage transcriptional regulators as reactive markers and mediators of disease. We are performing studies to determine their clinical utility as markers and to elucidate their role as disease mediators using patient samples and model systems.