Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells

Abstract

Abstract-The ideal way to prevent and cure atherosclerosis and the subsequent end organ damage is to restore and rejuvenate the dysfunctional vasculature and the damaged organs. Various studies have underlined the important role of bone marrow-derived endothelial progenitor cells (EPCs) in vasculogenesis and angiogenesis of ischemic tissue, but only a few studies have concentrated on the role of EPCs in the prevention and therapy of atherosclerosis. Extended endothelial cell damage by cardiovascular risk factors can result in endothelial cell apoptosis with loss of the integrity of the endothelium. The consequences are an increased vascular permeability of the endothelium followed by facilitated migration of monocytes and vascular smooth muscle cell proliferation, resulting in the premature manifestation of an atherosclerotic lesion. A growing body of evidence suggests that circulating EPCs play an important role in endothelial cell regeneration. Systemic transfusion or intrinsic mobilization of EPCs enhances the restoration of the endothelium after focal endothelial denudation, resulting in a diminished neointima formation. In mice with atherosclerotic lesions, bone-marrow-derived stem cells are able to reduce atherosclerotic plaque size. However, various studies have demonstrated that in humans, cardiovascular risk factors impair number and function of EPCs, potentially restricting the therapeutic potential of progenitor cells. The current review focuses on the role of cardiovascular risk factors on endothelial cell apoptosis and EPCs with its pathophysiological consequences for atherogenesis and a regenerative therapy approach and will highlight the role of EPCs as a marker for cardiovascular mortality and morbidity. Clinical manifestations of atherosclerosis include myocardial infarction, heart failure, stroke, and peripheral artery disease, resulting in irreversible organ damage. Current guidelines for the prevention of atherosclerotic disease focus on lifestyle modifications and risk factor reduction and to minimize devastating factors such as free oxygen radicals and the subsequent endothelial cell (EC) damage. The recently published INTERHEART study has demonstrated that 9 easily measurable cardiovascular risk factors are associated with Ͼ90% of the risk of an acute myocardial infarction in a large global case-control study. 1 Accumulation of risk factors such as smoking, hypertension, and diabetes increased the odds ratio for acute myocardial infarction to 13.01 (99% CI, 10.69 to 15.83) compared with patients without these risk factors. Although the correlation between risk factors and atherosclerosis and resulting myocardial infarction is well known, compliance with lifestyle

Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

“…7,18 Human PROM1 is expressed by various stem and progenitor cells originating from diverse sources. 23 Owing to the role of EPCs in vascular and endothelial function, 24 we investigated these characteristics in five carriers of the R373C mutation. We found that the number of CECs, endothelial markers such as CD133, as well as the ability of EPCs to form endothelial colonies fell within the normal range in the tested patients.…”

FSP-1 Silencing in Bone Marrow Cells Suppresses Neointima Formation in Vein Graft

“…The transplant was created by injecting 5ϫ10 6 BM cells into the lateral tail vein of lethally irradiated (1100 rads) mouse recipients.…”

“…Inserts were placed over 24-well plates coated with a thin layer of 1% agarose in 1ϫ PBS to facilitate removal of transmigrated cells for further analysis. Freshly isolated BM cells (2ϫ10 6 ) from WT or FSP-1-GFP ϩ mice were added to the top chamber and allowed to transmigrate through HUVEC at 37°C. After 3 or 24 hours, the top chamber was removed and the cell number in the bottom chamber was determined using a Z1 Beckman Coulter counter (Beckman Coulter, Fullerton, CA) GFP ϩ cells were counted using fluorescent microscope.…”

“…For analysis of invasion, collagen gel (100 L) (Millipore Corp, Billerica, MA) was added to the transwell insert and kept at 37°C to solidify the gel. BM cells (2ϫ10 6 ) from WT or FSP-1-GFP ϩ mice were added to the gels; after culturing for 7 days, cells on the membrane were fixed and counterstained with DAPI. The total number of cells and the number of GFP ϩ cells were counted using a fluorescent microscope.…”

“…6,7 In AV grafts, BM-derived, c-Kit-positive cells can assume the phenotype of either VSMC or endothelial cells, as determined by the expression of calponin or endothelial nitric oxide synthase, respectively. 7 BM-derived cells can also assume other roles including conversion into inflammatory or progenitor cells that participate in the formation of neointima in AV grafts.…”