How vessels narrow

Vascular narrowing, the clinical dilatation of narrowed vessels, and the restenosis of those vessels are central topics in modern cardiology. This review discusses the cellular basis both for the spontaneous narrowing of vessels and for the restenotic process that occurs after angioplasty. The central issue, as discussed in this review, is likely to be remodeling of the vessel wall rather than simple accretion of lipid mass in atherosclerosis or simple physical dilatation following angioplasty. While it is true that the atherosclerotic lesion grows by accretion of lipid mass, this by itself does not narrow vessels. As we will discuss, the vessel has a phenomenal ability to accommodate changes of this sort. Narrowing must occur, at least in part, because of a failure of this normal ability to accommodate. In a similar manner, one might expect the restonotic vessel to simply remodel itself down to its preangioplasty size. The issue for cell and molecular biologists is what "remodeling" means. Until recently, the assertion has been that remodeling occurred as the result of the formation of new intimal mass; that is, the atherosclerotic vessel was seen as returning to its original dimensions following angioplasty as a result of forming a new intimal mass that filled in the dilated space. Recent studies using cell kinetic methods as well as intravascular ultrasound, however, have cast doubt upon this hypothesis. It now appears that the loss of gain following angioplasty is likely to be due to the formation of new tissues which remodel the vessel wall without necessarily adding mass to it. This is the same sort of process that is well described in wound healing. The nature of this new tissue is of great interest. Studies in this laboratory and others have identified genes which may be unique to this tissue and explain the remodeling response.