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 (100mg/ml) for 24h to induce a model of EPC dysfunction invitro, 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.