Cellular Heterogeneity of the Vascular Tunica Media

The Problem Following arterial injury in adult humans and other mammals, there occurs a thickening of the intimal layer of the vessel wall due to migration of cells from the tunica media and proliferation of these migrated cells, along with any resident intimal cells.This intimal thickening, or neointimal formation, can lead to vessel stenosis or even occlusion and is the cellular basis of all intimal vascular disease.An understanding of this process leading to prevention, retardation, or reversal of intimal thickening would dramatically reduce morbidity and mortality from vascular disease.The identity of the cells involved in intimal thickening has not been conclusively determined.The morphology, growth properties, and protein expression of cells in the thickened intima are distinct from those of vascular smooth muscle cells within the tunica media or of endothelial cells lining the vessel lumen.There are at least three hypotheses to explain the identity of neointimal cells: (1) They arise from fully differentiated vascular smooth muscle cells within the tunica media.During their migration to and proliferation in the intimal layer, they undergo function-specific modifications, thus acquiring the characteristics ascribed to neointimal cells.(2) They arise from a normally resident population of smooth muscle "stem cells."Such cells may be embryonic or fetal smooth muscle cells that have not fully differentiated or a multipotential cell that could form either neointimal or smooth muscle cells.Unlike differentiated smooth muscle cells, these cells would retain the ability to migrate and proliferate.During migration to and subsequent proliferation within the thickening intima, such cells may acquire additional characteristics of neointimal cells.(3) They arise from a cell lineage within the tunica media that is distinct from that of the smooth muscle cell.The characteristics of these cells may be modulated to those of neointimal cells during the process of intimal thickening.Because these hypotheses are not mutually exclusive, a combination of the three is also possible.The intent of this brief review