Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting

Abstract

Objectives: The effect of patient age on circulating endothelial progenitor cells (EPCs) and their mobilization during coronary artery bypass grafting (CABG) was assessed.

Background: The EPCs are able to contribute to reparative neovascularization after tissue ischemia. In experimental models, reparative neovascularization is impaired in senescent animals, but the role of EPCs in this impairment, especially in humans, is unknown.

Methods: In 50 consecutive patients (43 to 80 years old) with stable coronary artery disease undergoing CABG, the numbers of EPCs and the plasma levels of interleukin (IL)-6, IL-8, IL-10, and IL-18, as well as vascular endothelial growth factor (VEGF) and placental growth factor, were determined preoperatively, after coming off bypass, and 6, 12, 24, and 72 h postoperatively.

Results: Preoperative values of EPCs were lowered with increasing age, similar to the lowering of plasma VEGF levels. These age-associated decreases could not be explained by differences in atherosclerotic risk factors or cardiac function. Bypass surgery induced a rapid mobilization in EPCs, IL-6, IL-8, IL-10, and VEGF, with a peak 6 h postoperatively. Persistently lower levels of EPCs and VEGF throughout the observation period were observed in patients >69 years old, which could not be explained by differences in the operative procedure or inflammatory IL activation.

Conclusions: Despite a significant increase in EPCs and release of cytochemokines during CABG, age is a major limiting factor for mobilization of EPCs. Further studies are necessary to improve the strategies for mobilization, ex vivo expansion, and re-transplantation of EPCs in aging patients.