Effect of long-term exercise on endothelial progenitor cells in healthy humans
Hagberg, James M
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Endothelial progenitor cells (EPCs) are derived from the bone marrow and have been found to play a role in postnatal neovascularization and re-endothelialization. Reduced EPC number and function have been associated with death from cardiovascular diseases, CVD risk factors, and endothelial dysfunction. Oxidative stress, specifically, oxidized LDL (OxLDL) has been shown to decrease EPC number and function, and increase EPC senescence in vitro. Regular physical activity is related to lower rates of CVD; however the mechanisms underlying the benefits of exercise in the prevention of CVD are not fully clear. Exercise may improve the number, and function of EPCs while improving oxidative stress status. The primary purpose of this study was to compare CD34+/KDR+ EPC number, EPC clonogenic capacity, and senescence, in healthy men that have participated in greater than 20 years of moderate- to high-intensity exercise with low-active control subjects. To assess the effect of physical inactivity on these markers, a subset of exercisers (n=10) stopped exercising for 10 days after which, measures of EPC number, colony forming units, and senescence, endothelial function and oxidative stress were re-evaluated. Results showed that, CD34+/KDR+ cell number, CFU-Hill colonies, and EPC senescence were not statistically different between athlete and control groups. CD34+/KDR+ cell number was closely related to endothelial function. Specifically, the forearm blood flow response to reactive hyperemia was correlated with CD34+/KDR+ number in sedentary participants. Additionally, 5 athletes significantly decreased their CD34+/KDR+ number, which was related to a significant decline in endothelial function, indicating that regular physical activity is important for some athletes to maintain healthy endothelial function, perhaps through the maintenance of elevated number of circulating CD34+/KDR+ cells. CFU-Hill colony number was strongly correlated with hyperemic blood flow response in control participants and related to oxLDL independent of physical activity status. Athletes who participated in 10-days of exercise detraining demonstrated a significant decrease in EPC senescence, which was related to improved total antioxidant capacity. Overall, these results show that CD34+/KDR+ number is closely related to endothelial function. Moreover, the function of EPCs appears to be affected by oxidative stress and antioxidant availability.