Cardiovascular disease: Increasing evidence indicates that during the aging process, arteries become occluded due to a defective wound repair mechanism in the artery wall. Our current studies are examining several pathways by which human vascular cells can become resistant to the natural inhibitors and apoptotic factors that should control their survival and expansion after vascular injury. Some of these pathways appear to be similar to heat shock proteins, which confer resistance to a broad range of agents. It is hoped that by understanding the mechanisms of resistance, it will be possible to intervene, and restore responsiveness to the natural control mechanisms. Current studies are also examining the diagnostic and therapeutic value of the newly identified cardiovascular risk factor gene located at chromosome 9p21.
Genomics: Genomic technology is one of the main tools for identifying mechanisms of resistance to apoptosis. By comparing the expressed genomes from cells that are sensitive to apoptosis with cells that are resistant, we are identifying genes associated with resistance. GeneChip arrays can scan up to 12,000 genes simultaneously, and report changes of less than 2-fold in the mRNA levels. In collaborative studies, we have used similar strategies to examine hypoxia-inducible genes, statin-regulated genes, tumor-related genes, and age-related changes in gene expression, among others.
Stem Cells: The major health impact of vascular disease is the potential for myocardial infarction, which causes focal death of the myocardium in the ischemic region. The regenerative ability of cardiomyocytes appears to be quite limited, leading to chronic cardiac insufficiency. In prior studies, we have demonstrated that autologous adult stem cells can be used to partially repair the damaged myocardium. Current studies are optimizing different methods of obtaining adult human stem cells, and examining methods of improving their conversion to cardiomyocytes.