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Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures

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TLDR
It is suggested that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events.
Abstract
Background— The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. Methods and Results— EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% (P<0.01) and inversely correlated with patient levels of hemoglobin A1C (P<0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-α (TNF-α) (P<0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls (P<0.05). Conclusions— These findings suggest that type II ...

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Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1

TL;DR: It is shown that SDF-1 gene expression is regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) in endothelial cells, resulting in selective in vivo expression of S DF-1 in ischemic tissue in direct proportion to reduced oxygen tension.
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Endothelial Progenitor Cells: Characterization and Role in Vascular Biology

TL;DR: This review summarizes the mechanisms regulating endothelial progenitor cell–mediated neovascularization and reendothelialization and describes the characterization of the different progenitors cell populations.
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Mechanisms of Diabetic Complications

TL;DR: The well validated, as well as putative mechanisms involved in the development of diabetic complications are discussed and new fields of research, which warrant further investigation as potential therapeutic targets of the future, will be highlighted.
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Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors

TL;DR: The findings suggest that acetylated LDL(+)ulex-lectin(+) cells, commonly referred to as EPCs, do not proliferate but release potent proangiogenic growth factors, which may allow for development of novel angiogenic therapies relying on secreted growth factors or on recruitment of endogenous monocytes/macrophages to sites of ischemia.
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Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration.

TL;DR: Identification of factors that promote differentiation of the progenitor cells will permit functional incorporation into neo-vessels of specific tissues while diminishing potential toxicity to other organs.
References
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Journal ArticleDOI

Isolation of putative progenitor endothelial cells for angiogenesis.

TL;DR: It is suggested that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarianAngiogenesis.
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Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

TL;DR: The data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
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Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization

TL;DR: Findings indicate that postnatal neovascularization does not rely exclusively on sprouting from preexisting blood vessels (angiogenesis); instead, EPCs circulate from bone marrow to incorporate into and thus contribute to postnatal physiological and pathological neov vascularization, which is consistent with postnatal vasculogenesis.
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Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease

TL;DR: Patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD, and hypertension was identified as a major independent predictor for impaired EPC migration.
Journal ArticleDOI

Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.

TL;DR: Ex vivo expanded hEPCs may have utility as a "supply-side" strategy for therapeutic neovascularization in mice with hindlimb ischemia and the rate of limb loss was significantly reduced.
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