The impact of progenitor cells in atherosclerosis

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During the pathogenesis of arteriosclerosis, endothelial cells on the arterial wall damaged by various means were initially thought to be replaced by replication of neighboring cells. Smooth-muscle cells (SMCs) were also thought to migrate from the media into the intima, where they constituted arteriosclerotic lesions. This concept has been challenged, however, by the discovery that progenitor cells in the circulation and adventitia contribute to endothelial repair and SMC accumulation. Studies have demonstrated that atherosclerosis is a pathophysiologic process initiated by endothelial death in specific areas, such as bifurcation regions, and with subsequent replacement by endothelial progenitor cells. Differentiation of the neoendothelial cells into mature endothelium takes several days or weeks, during which LDL deposits in the intima. Blood mononuclear cells also adhere to neoendothelial cells and migrate into the subendothelial space. Meanwhile, progenitor cells from blood and the adventitia migrate into the intima, where they proliferate and differentiate into neo-SMCs. All risk factors for atherosclerosis can exert their effects on the vessel wall partly via increase in endothelial turnover, inhibition of progenitor-cell differentiation, and promotion of smooth-muscle and macrophage accumulation in lesions. Thus, progenitor cells comprise the main cell source responsible for the formation of atherosclerotic lesions, which appear in the context of inflammatory disease. Here I provide an update on research and discuss the role of progenitor cells in the pathogenesis of atherosclerosis.

Key Points

  • Endothelial damage, dysfunction or both are critical events in the initiation of atherosclerotic-plaque development, and regeneration is of particular importance

  • Progenitor cells are a likely source of endothelial repair and smooth-muscle accumulation in atherosclerotic lesions

  • Bone-marrow-derived endothelial progenitor cells are mobilized to re-establish an intact endothelial layer following denudation of endothelium

  • The homing mechanisms responsible for recruitment of endothelial progenitor cells to the damaged vessel surface or for angiogenesis within the vessel wall need to be investigated

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Figure 1: En face photographs showing endothelial cells of mouse aortas.
Figure 2: Schematic representation of the initiation of atherosclerosis.
Figure 3: En face staining of aortic endothelial cells with a substrate X-galactosidase to show the recipient origin after grafting.
Figure 4: Schematic representation of progression of atherosclerosis.


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I acknowledge all collaborators who contributed to the work summarized in the review. I thank Dr E Torsney for critical reading of the manuscript. This work was supported by grants from the British Heart Foundation, Oak Foundation and the European Community's Sixth Framework Programme for Research.

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Correspondence to Qingbo Xu.

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