Endothelial Progenitor Cells

Abstract

See related article, pages 1379–1388 Endothelial dysfunction is a hallmark of cardiovascular and cerebrovascular disease. Restoring the endothelial lining to normal is critical for slowing or reversing the progression of vascular disease. The progression of endothelial regeneration following mechanical disruption and its effect on vascular function has been described in normal porcine coronary arteries in the absence of risk factors for vascular disease.1–3 Despite regrowth of endothelium in arteries shortly after denudation, the endothelium was morphologically different. Smooth muscle function remained normal but endothelium-dependent relaxation progressively worsened over several weeks. Although these early studies assumed that the regeneration of the endothelial lining was because of the migration and proliferation of neighboring cells, the proliferation rate of endothelial cells is low.4 We now know that alternative repair mechanisms contribute to the regrowth of endothelium. Recent studies suggest that a damaged endothelial lining can be restored by endothelial progenitor cells (EPCs). Circulating EPCs derived from bone marrow contribute to the repopulation by seeding the intimal lining with new cells.4–6 These circulating EPCs home in on injured areas and accelerate the regeneration of new endothelium. In culture, EPCs acquire both morphological and functional characteristics of endothelial cells expressing von Willebrand factor, CD31, and KDR, a receptor for vascular endothelial growth factor (VEGF).4 They release nitric oxide, form tube-like structures in vitro and enhance neovascularization and blood flow in ischemic hindlimb in vivo.7 Thus EPCs provide a potential new approach to repair vascular injury and reverse the progression of vascular disease. Although EPCs promote endothelial regeneration and angiogenesis, atherosclerosis is not limited to damage of the endothelial lining. Activation of an inflammatory response induces infiltration of monocytes and smooth muscle proliferation contributing to the development of atherosclerotic lesions.4 Risk factors including hyperlipidemia, …