Induction of Vascular Atrophy As a Novel Approach to Treating Restenosis. A Review

Regardless of the type of arterial reconstruction, luminal narrowing (stenosis or restenosis) develops in approximately one third of the vessels. In the past, the focus of research has been on the mechanisms of stenosis (intimal hyperplasia, pathologic remodeling) and pharmacologic approaches to prevention. An alternative approach is to induce intimal atrophy after luminal narrowing has developed, thus limiting treatment to only those patients that develop a problem. This approach to treat established disease by reducing wall mass through induction of cell death and extracellular matrix removal would be particularly useful for treating stenosis in synthetic bypass grafts or stented vessels, in which intimal hyperplasia is the primary mechanism of stenosis. This approach may be applicable as well to other vascular proliferative disorders, such as pulmonary hypertension and chronic transplant arteriopathy. Proof of principle has been shown in experiments with antibodies to platelet-derived growth factor (PDGF) receptors that cause neointimal regression in baboon polytetrafluoroethylene (PTFE) grafts and with angiotensin-converting enzyme inhibitors that induce medial atrophy in hypertensive arteries. Possible molecular targets could include PDGF receptors, A20, and BMP4. Further studies are needed to determine the utility of such a therapeutic approach to vascular disease.