Progenitor cell-derived smooth muscle cells in vascular disease

Accumulation of vascular smooth muscle cells (VSMCs) in the tunica intima plays a major role in the pathogenesis of atherosclerosis and restenosis following endovascular procedures. Arterial VSMCs are heterogeneous even in the normal vessel wall and display different phenotypes in physiological and pathological conditions. In the classical paradigm, vascular wall injury induces VSMC de-differentiation, proliferation and migration from the media into the intima in response to growth factors and proteolytic agents. Accordingly, VSMCs in atherosclerotic plaques and in restenosis display a de-differentiated or 'synthetic' phenotype compared to a 'contractile' phenotype in the normal media. In contrast, recent studies have identified bone marrow and peripheral blood-derived endothelial and VSMC progenitors that may contribute to intimal formation in atherosclerosis, after arterial injury and in transplant atherosclerosis. The precise frequency of these bone marrow-derived vascular precursor cells is controversial and their role is unknown. In addition, additional data support the presence of a resident progenitor cell subpopulation and its involvement in the response of the adult arterial wall to damage or ischemia. This review will examine the evidence for and the putative role of progenitor cell-derived VSMCs in arterial disease, a necessary prerequisite before deciding whether progenitor cells are therapeutic targets in vascular disease.