Downregulated GTCPH I/BH4 Pathway and Decreased Function of Circulating Endothelial Progenitor Cells and Their Relationship with Endothelial Dysfunction in Overweight Postmenopausal Women

Abstract

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.