The Effects of Lipoprotein on Endothelial Progenitor Cells Function and Endothelial-to-Mesenchymal Transition Process

In 1997, T. Asahara et al. discovered the circulating endothelial progenitor cells (EPCs) which is derived from bone marrow. The circulating EPCs in the peripheral blood may replenish the denuded endothelium and involve in neo-vasculogenesis. Thus, on the view points of recovery of endothelial function, maintaining the integrity of vessel wall and the function of neo-angiogensis, the roles of EPCs have gained lots of attention. The number and function of EPCs may be influenced by atherosclerotic risk factors, such as oxidative stress, hypertension, hyperlipidemia, and diabetes mellitus. Additionally, recently reports demonstrated that inflammatory cytokines and transforming growth factor (TGF)-β may induce the process of endothelial-to mesenchymal transition (endoMT) and promote the differentiation of endothelial cells to vascular smooth muscle-like cells which mediating the intimal hyperplasia during atherogenesis. Especially, high level of oxidized low-density lipoprotein (oxLDL) had been shown to accelerate endothelial dysfunction and atherosclerotic formation. However, the actual roles of high density lipoprotein (HDL) and oxLDL on EPCs functions has rarely been investigated. Recently, under the support of NSC from Taiwan, our group had announced that HDL from healthy subjects may potentiate EPCs function in low concentration (10-20 mg/dL). Paradoxically, HDL in normal to high physiological concentration (40-80 mh/dL) would impair EPCs function through the pathway of Rho kinase activation. In 2013, we investigate the effects of oxLDL on EPCs function and the underlying mechanisms. However, it important to interpret the influence of dyslipidemia on atherosclerosis with the knowledge of the interactions between HDL and oxLDL on EPC functions. In addition, defective HDL had gradually gained focus recently resulting from it dysfunction and disturbance. Therefore, in this project, we plan to spend 3 years to explore the functions and endoMT of EPCs in HDL/oxLDL co-existence environment using in vivo animal and in vitro cultured EPCs studies. Additionally, we plan to investigate the influence of defective HDL from type 2 diabetes mellitus or end stage renal disease (ESRD) patients on EPCs function an endoMT through clinical observation and in vitro study. We also believe the results of our study will provide the more effective treatment protocols for patients with dyslipidemia in the future.