Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries.
ABSTRACT Circulating endothelial progenitor cells (EPCs) play an important role in repair of injured vascular endothelium and neovascularization. The present study was designed to determine the effect of EPCs transplantation on the regeneration of endothelium and recovery of endothelial function in denuded carotid arteries.
Isolated mononuclear cells from rabbit peripheral blood were cultured in endothelial growth medium for 7 days, yielding EPCs. A rabbit model of common carotid artery denudation by passage of a deflated balloon catheter was used to evaluate the effects of EPCs on endothelial regeneration and vasomotor function. Immediately after denudation, autologous EPCs (10(5) cells in 200 microL saline) or 200 microL saline alone (control) were administered into the lumen of injured artery.
Four weeks after transplantation, fluorescence-labeled colonies of EPCs were found in the vessel wall. Local transplantation of EPCs as compared with saline administration accelerated endothelialization and significantly improved endothelium-dependent relaxation when assessed 4 weeks after denudation (n=4 to 5, P<0.05). Transplantation of EPCs did not affect vasomotor function of arterial smooth muscle cells. Protein array analysis of conditioned media obtained from cultured EPCs demonstrated the ability of these cells to produce and release a number of proangiogenic cytokines.
We conclude that local delivery of cultured circulating EPCs into the lumen of denuded carotid arteries accelerates endothelialization and improves endothelial function. Paracrine effects of EPCs may contribute to regenerative properties of EPCs.
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Article: Chemokines and atherosclerosis.[show abstract] [hide abstract]
ABSTRACT: Chemokines or chemotactic cytokines represent an expanding family of structurally related small molecular weight proteins, recognised as being responsible for leukocyte trafficking and activation. Soon after the discovery of this class of cytokines, about a decade ago, monocyte chemoattractant protein-1 (MCP-1) was found to be highly expressed in human atherosclerotic lesions and postulated to be central in monocyte recruitment into the arterial wall and developing lesions. In this review, we will discuss our present knowledge about MCP-1 and its receptor CCR2 and their role in atherogenesis. Although less well established, other chemokines such as RANTES, MIP-1alpha and MIP-1beta have also been implicated in atherosclerotic lesion formation as are a number of more recently discovered chemokines like MCP-4, ELC and PARC. The role of these chemokines in the progression of atherosclerosis will be discussed as well as the emerging role of IL-8, mostly know for its effects on neutrophils. Particular attention will be given not only to the involvement of chemokines in the inflammatory recruitment of monocytes/macrophages, but also to their role in the related local immune responses and vascular remodelling which occur during the formation of unstable atherosclerotic plaques.Atherosclerosis 01/2000; 147(2):213-25. · 3.71 Impact Factor
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ABSTRACT: Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO also has activity on hematopoietic lineages other than megakaryocytes. However, little is known about the effects of TPO on nonhematopoietic cells expressing the TPO receptor, such as endothelial cells (EC). We have previously shown that specific murine liver EC (LEC-1) located in the hepatic sinusoids coexpress TPO and its receptor, c-mpl. Likewise, we showed that TPO has a proliferative effect on LEC-1. In this study, we have further examined the effects of TPO on other biological functions of LEC-1. Stimulation with TPO induced secretion of proinflammatory cytokines (i.e., IL-1beta, IL-6, TNF-alpha) from LEC-1. TPO-induced proliferation of LEC-1 was synergistically enhanced with the addition of TNF-alpha. TPO also induced the proliferation of LEC-1 in the presence of IFN-gamma, which alone inhibited the growth of these cells. TPO has no effect on other endothelial cell functions such as nitric oxide production and adhesion molecule expression. These observations establish a novel activity of TPO on murine liver endothelial cells in terms of inducing cytokine production by these cells. Our results suggest that this cytokine may act synergistically with other cytokines to induce LEC-1 proliferation.Microvascular Research 10/1999; 58(2):108-13. · 2.93 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) has been shown to promote neovascularization in animal models and, more recently, in human subjects. This feature has been assumed to result exclusively from its direct effects on fully differentiated endothelial cells, i.e. angiogenesis. Given its regulatory role in both angiogenesis and vasculogenesis during fetal development, we investigated the hypothesis that VEGF may modulate endothelial progenitor cell (EPC) kinetics for postnatal neovascularization. Indeed, we observed an increase in circulating EPCs following VEGF administration in vivo. VEGF-induced mobilization of bone marrow-derived EPCs resulted in increased differentiated EPCs in vitro and augmented corneal neovascularization in vivo. These findings thus establish a novel role for VEGF in postnatal neovascularization which complements its known impact on angiogenesis.The EMBO Journal 08/1999; 18(14):3964-72. · 9.82 Impact Factor