Coronary heart disease is the leading cause of death in the developed world. This disease results from atherosclerosis or fatty deposits in the vessel wall that causes blockage of coronary arteries, causing shortage of blood supply with consequent heart attacks, sudden death, or heart failure. To restore coronary blood supply, physicians use guide-wires to position an inflatable balloon at the blockage site of the artery, where the balloon is inflated to open the artery. This angioplasty procedure is usually accompanied by the placement of a metal stent at the diseased site to maintain vessel opening. Such percutaneous coronary intervention (PCI) with angioplasty and stenting is the dominant procedure for opening obstructed coronary arteries. However, PCI activates a population of cells in the vessel wall to grow into the vessel lumen, causing re-narrowing of the artery. This vessel re-narrowing (restenosis) is the major hurdle limiting the success of PCI. Mental stents coated with drug inhibitors of cell growth (drug eluting stents, or DES) reduce re-narrowing; however, considerable concerns have emerged regarding the safety of DES due to an increased risk of sudden stent occlusion by platelet aggregates (or thrombosis) and the need for prolonged anti-platelet therapy, which poses bleeding risks especially to older patients or patients who need surgery. These concerns call for defining mechanisms that control re-narrowing of injured arteries.
A population of cells resident in the vessel wall consists of stem cells that are activated when vessels are injured. Activation of these cells directly contributes to vessel re-narrowing. Our goal is to understand how these cells are activated by vessel injury, how injury signals these cells to divide and invade the vessel lumen, what molecular effectors control the cellular responses, and how to intercept these signals and effectors to prevent vessel re-narrowing. In the past year, we successfully developed new methods for isolating and growing these vascular stem cells in test tubes. These new methods allowed us to determine how these stem cells turn into other types of vessel cells after injury and how they contribute to re-narrowing of injured vessels. We are using this method to define molecular pathways that control vessel wall stem cells to respond to vessel injury.