Cardiovascular diseases, which represent the most important cause of mortality and morbidity in industrialized societies, result from complex interactions between several types of risk factors resulting from either genetic variation or environmental conditions (such as life style). It is known that the mass of the cardiac left ventricle is: 1) determined for a great part (60-80%) by heritable genetic factors, and 2) correlates tightly and in a linear fashion with cardiovascular morbidity and mortality in human populations. We surmise that by finding which genetic variants are responsible for left ventricular mass, we will also be able to find genetic factors that increase cardiovascular risk.
We thus study in our laboratory genetic crosses of inbred animal strains. By integrating information about cardiac phenotypic traits, microarray-derived tissue gene expression levels and genetic maps, we are attempting to elucidate which genes or groups of genes are responsible for left ventricular mass. These results are then either validated by biologic studies in animal models or further extended by studying the contributions of the same genes in human populations. Finally, we are studying how these genes interact with epigenetic and/or environmental factors to shape cardiac phenotypic traits.