The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.

Abstract-Endothelial cell damage is one important pathophysiological step of atherosclerosis and restenosis after angioplasty. Accelerated reendothelialization impairs neointima formation. We evaluated the role of intravenously transfused endothelial progenitor cells (EPCs) on reendothelialization and neointima formation in a mouse model of arterial injury. 4 or transplanted stem cells 5-9 on remodeling after myocardial infarction. Special attention has been directed to endothelial progenitor cells (EPCs), a subset of BM-derived progenitor cells, which have been shown to play an important role in (patho-)physiological neoangiogenesis 1,10 -15 and vascular regeneration after myocardial infarction. 8,13,16 -18 The role of stem cells and BM-derived progenitor cells in atherosclerosis, the underlying reason for myocardial infarction and tissue damage, remains unclear. Atherosclerotic lesion formation is initiated by endothelial cell damage leading to endothelial dysfunction. Apoptosis of endothelial cells, macrophage adhesion and invasion, and smooth muscle cell migration and growth finally lead to stenosis of the targeted vessel. 19 Accelerated reendothelialization effectively impairs smooth muscle cell proliferation and neointima formation 20,21 and is therefore of special interest with regard to prevention of the early stages of atherosclerosis and restenosis after angioplasty. 22 It has been shown that the number of circulating EPCs inversely correlates with risk factors for atherosclerosis 23,24 and that risk factors such as diabetes impair the migratory capacity of EPCs. 25 Furthermore, reduced levels of EPCs are associated with endothelial dysfunction as determined by flow-mediated brachial-artery reactivity. 24 We and others have recently demonstrated that BM-derived progenitor cells significantly contribute to reendothelialization after endothelial cell injury. Mobilization of EPCs to the circulation by statins is associated with an enhanced reendothelialization and decreased neointima formation, resulting in a reduction of restenosis. 26,27 However, it could not be excluded that the demonstrated beneficial effects were exerted by statin therapy rather than EPC mobilization. To provide evidence that EPCs are involved in vascular remodeling, we evaluated the possible impact of intravenously transfused EPCs on reendothelialization and neointima formation in a mouse model of arterial injury.

Abstract-Our goal was to identify functionally important subpopulations within the heterogenous group of endothelial progenitor cells (EPC). Fluorescence-activated cell sorter analysis of CD133 ϩ progenitor cells revealed the presence of CD34 ϩ and CD34 Ϫ subpopulations. CD34 Ϫ /133 ϩ progenitors differentiate into CD34 ϩ /133 ϩ EPC, adhere more potently than these in response to SDF-1, and rapidly home to sites of limb ischemia in human volunteers. In human coronary atherectomy samples, fewer CD34Ϫ /133 ϩ than CD34 ϩ /133 ϩ EPC are present in stable plaques, whereas cell numbers increase with a reversion of the ratio in unstable lesions. In CD34 Ϫ /133 ϩ EPC-injected nude mice, more transplanted cells coexpressing endothelial markers home to carotid artery lesion endothelium than in CD34 ϩ /133 ϩ -injected mice. In the former, lesions were smaller and reendothelialization higher than in the latter. We identified a new CD34 Ϫ /133 ϩ EPC subpopulation, which is apparently a precursor of "classical" CD34 ϩ /133 ϩ EPC, and functionally more potent than these with respect to homing and vascular repair. (Circ Res. 2006;98:e20-e25.)

The level of circulating CD31+/Annexin V+ MPs is an independent predictor of cardiovascular events in stable CAD patients and may be useful for risk stratification.