The Influences and Underlying Mechanisms of Differentiation and Proliferation in Ox-Ldl and Hdl-Stimulated Human Late-Outgrowth Endothelial Progenitor Cells.

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Atheroscerlotic cardiovascular disease, which includes atherothrombosis, atherosclerotic plaque embolization and vascular occlusion and tissue ischemia, is beyond doubt, one of the leading causes of death in modern society. Several risk factors, like, hypertension, type 2 diabetes, dyslipidemia, smoking, and older ages are all contributors to this illness. The thin lining of the inner vessel wall, the endothelium, plays the important role as a house-keeper to maintain the integrity of the vasculature, either functionally or structurally. Before the existence of the full-brown atherosclerotic cardiovascular disease, endothelial dysfunction may have been existed for a long period of time. The replacement of denuded endothelium and neo-angiogenesis were also though to be replaced and replenished by the new divided endothelial cells near by. However, in 1997, T. Asahara and colleagues raised the concept of endothelial progenitor cells (EPC) and proved that the so called EPC, which was mobilized from the bone marrow and circulate in the peripheral blood may help the replenishment of the denuded endothelium and the neo-vasculogenesis in hind limb ischemic mouse model, which had changed the previous concepts of endothelial repair and neo-angiogenesis. Thus, on the view points of recovery of endothelial function, maintaining the integrity of vessel wall and the function of neo-angiogensis, the role of EPC has gained lots of attention. According to recent researches, EPC could be further divided into two categories: the early and late out-growth EPCs. By far, few researches had focused on the late out-growth EPCs, and which was thought to possess the more potential to differentiate into the mature endothelium under appropriate manipulations than the early EPCs. A little bit unlike stem cells, the EPCs may also be influenced by some environments factors, for example, oxidative stress, which may results in reducing the numbers of mobilized circulating EPCs and also their functions for neovascularization. Clinical studies had proved that patients with more cardiovascular risk factors may have reduced circulating EPC numbners and function. The circulating EPC numbers is also proved as a predictor of cardiovascular prognosis. Currently, from the view points of tissue engineering, ways to manipulating EPC, either in the circulating numbers or functions EPCs, or to rejuvenate the functionally-impaired EPCs are promising. Dyslipidemia is one of the cardiovascular risk factors. The high low-density lipoprotein, especially the oxidized one, has been shown to accelerate endothelial dysfunction and the formation of atherosclerosis. Besides, high level of high density lipoprotein, may reverse the situation, either by reverse transport of the cholesterol from peripheral tissue back to liver, or by acting on the scavenger receptor type B1, may act as a protection role in the vessel wall integrity by increasing NO production. Dyslipidemia may not only impair the function of mature endothelial cells but may also hamper the extent of neo-angiogenesis. Currently, the influences of ox-LDL and HDL on EPCs functions had rarely been addressed and not to mention the underlying mechanisms. In our study, we would like to investigate the influences of oxidized low density lipoprotein and high density lipoprotein on endothelial progenitor cells on EPC in different serum concentrations and we would also like to investigation the SR-B1, eNOs, LOX-1 receptor associated underlying mechanisms.
StatusFinished
Effective start/end date8/1/117/31/12