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31-03-2010 | Diabetes | Article

Hyperglycemia impairs endothelial cell revascularization properties

Abstract

Free abstract

MedWire News: Hyperglycemia and increased levels of oxidized lipids associated with diabetes and coronary artery disease (CAD) severely impair the migration of endothelial progenitor cells (EPCs) and, therefore, vascular regeneration, say scientists.

It is well established that the movement of EPCs from the bone marrow to areas where blood vessels have been damaged is a key part of neovascularization.

Recently, it has been suggested the mobilization of EPCs is mediated by various chemokines, cytokines, and growth factors, including stromal-derived factor-1α, a cytokine that stimulates the CXC receptor-4 (CXCR4) on the EPC membrane and activates the Pi3K/Akt/eNOS signaling pathway.

In line with this suggestion, it has been shown that reduced CXCR4 signaling explains why EPCs do not perform their neovascularization function adequately in mice with diabetic ischemia and in patients with CAD.

For the current study, Saher Hamed (Israel Institute of Technology, Haifa) and co-workers studied the effects of exposing EPCs to atherogenic, oxidized low-density lipoprotein (OxLDL) cholesterol,l and/or to hyperglycemic conditions.

Cells were isolated and cultured from 55 patients with Type 2 diabetes, some of who also had CAD, and 15 healthy volunteers who were matched for age and gender.

The authors discovered that in vivo EPC count, and in vitro EPC ability to migrate, CXCR4 expression, and nitric oxide production were all significantly reduced in patients with diabetes compared with healthy volunteers. These differences were even more pronounced when comparing patients with comorbid diabetes and CAD with healthy volunteers.

The investigators conclude in the journal Thrombosis Research: “Hyperglycemia and elevated circulating OxLDL in diabetes mellitus patients with CAD severely impair EPC migration and nitric oxide production.”

They add: “We suggest that either this pathway or the interaction between hyperglycemia and hyperlipidemia in patients with diabetes and CAD could be targeted therapeutically to rescue the impaired migration of EPCs and restore their neovascularization capacity.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Philip Ford