Although atherosclerosis is a systemic disease, comparative arteriographic and clinical studies have clearly demonstrated an almost complete freedom from atherosclerosis by the internal mammary artery. These blood vessels are remarkably resistant to atherosclerosis even when implanted into the coronary artery circulation as part of a coronary artery bypass procedure. Since the biologic reasons for the resistance of the internal mammary artery and the vulnerability of coronary arteries in a pro-atherosclerotic environment are not known, a research team lead by Dr. Behrooz Sharifi analyzed differential gene expression comparing the coronary artery to the mammary artery. His group found two genes, tenascin and pleiotrophin (PTN) genes, which are differentially expressed in the coronary artery.

Tenascin-C (TN) is an extracellular matrix protein that is prominently expressed during embryogenesis, but its expression is rarely detectable in adult tissues. TN, however, is re-expressed in diseases and in tissue injuries at sites where it is not normally expressed. While nothing is known about TN's function in vivo, several lines of evidence suggest that the rapid production of TN in inflamed tissues is aimed at controlling the spread of inflammation. Dr. Sharifi's team has devised in vitro and in vivo systems to investigate the role of this gene in cardiovascular disease.

Pleiotrophin (PTN), a pro-angiogenic gene, is differentially expressed in the coronary artery. While nothing is known about the expression and function of PTN in the cardiovascular system, there is extensive data about the activity of this molecule in cancer. It is thought that PTN promotes tumor vascularization by an angiogenic mechanism. Dr. Sharifi's team discovered that PTN induces the nucleus of monocytic cells to express a specific repertoire of genes, thereby modifying their identity into endothelial cells. The principal focus of Dr. Sharifi's research is to investigate the pathogenic role of PTN in cardiovascular disease and the potential therapeutic role of PTN on collateral growth of ischemic cardiovascular tissue.