The maintenance of vascular function has emerged as an important factor in keeping rates of cardiovascular disease (CVD) low. Endothelial progenitor cells (EPCs) are derived from the bone marrow and have been found to play a role in postnatal neovascularization (6) and re-endothelialization (106; 130). Reduced EPC number and function, including colony formation and migration, and increased senescence have been associated with death from cardiovascular diseases (133), CVD risk factors (126), future coronary events (103), and endothelial dysfunction (51). Oxidative stress has been proposed as a mechanism that decreases EPC number and function in vitro. In particular, oxidized LDL (OxLDL) has been shown to decrease EPC number and function (132), and increase EPC senescence (63) 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 (77; 77; 78), and function (54) of EPCs while improving oxidative stress status (127; 129).

The primary purpose of this study was to compare endothelial progenitor cell (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 age-matched 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 (AUC_1min ; r=-0.78, p=0.005). Additionally, 10 days of physical inactivity revealed 5 athletes who either had no change or an increase in CD34⁺/KDR ⁺ number and 5 athletes significantly decreased their CD34 ⁺/KDR⁺ number (70 ± 30% vs. -86 ± 7%, p=0.006). In athletes that decreased CD34⁺/KDR⁺ number with exercise training, the change in EPC number as significantly related to a decline in endothelial function (-25.7 ± 15.7% change in peak flow), 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, such that individuals with better endothelial function had enhanced EPC clonogenic capacity (r=0.84, p=0.001). CFU-Hill colony forming capacity was related to oxidized LDL independent of physical activity status; however, athletes who participated in 10-days of exercise detraining demonstrated a significant decrease in EPC senescence (22.8 ± 3.3 before vs. 16.4 ± 3.1% after training cessation, p=0.06), which was related to improved total antioxidant capacity (r=-0.66, p=0.04). Overall, these results show that while CD34⁺/KDR⁺ number is closely related to endothelial function and may be affected by exercise and inactivity, it is not influenced by oxidative stress whereas the function of EPCs appears to be affected by oxidative stress and antioxidant availability. These results may contribute to the understanding of the mechanisms involved in the maintenance of healthy endothelial function and prevention of cardiovascular disease.