Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury

Abstract

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.

c-kit-Immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions

“…Exactly how c-kit-immunopositive cells participate in this process is unknown; moreover, we cannot ignore the possibility that they may simply serve as an incidental marker of this disease process. Although we are unable to go beyond these postulates, there are circumstantial data in support of the notion that circulating progenitor cells may participate in vascular repair and lesion formation (3,10,23,25,32). However, as noted previously, the precise nature of endothelial and smooth muscle precursor cells and markers that might uniquely identify these cell types remains unclear (11).…”

“…Rehman and colleagues (24) suggest that the absence of specific endothelial or progenitor cell markers on cultured PBMCs gives reason to label these cells as cultured angiogenic cells (CACs), rather than EPCs. Recent studies show that intravenous transfusions of CACs mitigate neointima formation after vascular injury and prevent atherosclerosis in murine models (23,32).…”

Physical Activity in the Prevention and Treatment of Coronary Artery Disease

“…An elevated apoptotic rate of mature vascular endothelial cells in conjunction with an impaired regenerative capacity of CPC might further aggravate vascular alterations 55, 59, 60. Current knowledge of endothelial dysfunction in vascular disease is discussed in detail by Vanhoutte et al 61…”

Proteomic analysis of oxidative modification in endothelial colony-forming cells treated by hydrogen peroxide

“…Impaired function of EPCs is related to endothelial dysfunction (23). Some studies have indicated that EPCs are involved in repair of damaged endothelium and attenuate the development of atherosclerosis (24)(25)(26). Several pathological conditions, including hypertension, diabetes, and atherosclerosis, can impair the endothelial cell by oxidative stress (27).…”