p38 Mitogen-Activated Protein Kinase Downregulates Endothelial Progenitor Cells

Abstract
Background— Transplantation of endothelial progenitor cells (EPCs) improves neovascularization after ischemia, but patients with coronary artery disease (CAD) or diabetes mellitus show a reduced number of EPCs and impaired functional activity. Therefore, we investigated the effects of risk factors, such as glucose and TNF-α, on the number of EPCs in vitro to elucidate the underlying mechanisms. Methods and Results— EPCs of patients or healthy subjects were isolated from peripheral blood. Incubation with glucose or TNF-α dose-dependently reduced the number of EPCs (79.9±1.3% and 74.3±8.1% of control; P P P Conclusions— These results demonstrate that p38 MAP kinase plays a pivotal role in the signal transduction pathways regulating the number of EPCs ex vivo. SB203580 can prevent the negative effects of TNF-α and glucose on the number of EPCs and may be useful to improve the number of EPCs for potential cell therapy.

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