Age Dependent Expression of the Caridac Matrix

Burgess, Maria

Abstract

Despite advances in clinical cardiology, cardiovascular disease remains the leading cause of mortality in older individuals. Thus, research examining the mechanisms associated with maintaining cardiovascular health in older populations is of crucial importance. With the aging population increasing, and the noted importance of regular exercise in overall health maintenance and disease prevention, this proposal will characterize the results of advanced aging and chronic, aerobic training on the extracellular matrix (ECM) of the heart. ECM adaptations associated with aging and exercise are thought to contribute to diminished and enhanced heart function, respectively. In order to investigate how the cardiac ECM adapts to both aging and exercise-training , this project will : 1) establish a baseline of age-dependent expression of extracellular matrix (ECM) proteins and their integrin receptors in the heart, and 2) provide new and useful information on the ability of exercise to influence age associated changes in heart ECM structure. A variety of experimental approaches will be used to analyze these specific aims, including: 1) young, middle-aged and old mouse heart; 2) chronic exercise training (treadmill running); 3) analysis of cardiac mass, including mass of atrial and ventricular tissues; 4) biochemical analysis of total cardiac interstitial collagen and collagen phenotypes; 5) Western blot analysis for fibronectin and integrin protein; and 6) RNA extraction and ribonuclease protection analysis of gene (mRNA) expression of collagen types I and III, fibronectin and integrins. These experimental approaches will allow for the analysis of the association of ECM collagen, fibronectin and their integrin receptors with advancing age, as well as the ability of chronic, aerobic exercise to offset the detrimental adaptations known to occur. This project will also provide essential data for future investigations designed to test cellular and molecular mechanisms for age-associated and exercise-associated adaptations in cardiac function.