Involvement of endothelial nitric oxide synthase pathway in IGF-1 protects endothelial progenitor cells against injury from oxidized LDLs

Abstract

A high level of oxidized low-density lipoproteins (oxLDLs) is an independent risk factor for cardiovascular disease. The aim of the present study was to investigate whether insulin-like growth factor-1 (IGF-1) protected endothelial progenitor cells (EPCs) from injury caused by ox-LDLs, and whether the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway was involved in this process. EPCs were isolated from human peripheral blood and characterized. In order to evaluate the effect of IGF-1 on EPCs, cells were incubated with ox-LDLs (100 mg/ml) for 24 h to induce a model of EPC dysfunction in vitro, which demonstrated a decrease in the number of EPCs, concomitant with increased apoptosis and decreased proliferation rates. IGF-1 dose-dependently increased the number of EPCs. Concurrently, IGF-1 decreased the levels of apoptosis of EPCs and improved EPCs proliferation following ox-LDLs challenge. In addition, IGF-1 significantly increased NO levels in ox-LDLs-treated EPCs, accompanied by an upregulation in eNOS expression. The protective effects of IGF-1 on EPCs and NO production were abolished by L-NAME, a specific eNOS inhibitor. These results suggested that IGF-1 protects EPCs from dysfunction induced by oxLDLs through a mechanism involving the eNOS/NO pathway.