Abstract
PURPOSE: Exercise training partially restores endothelial function and exercise capacity in chronic heart failure (CHF) patients. Training-induced mobilization of endothelial progenitor cells (EPC) and their associated regenerative capacity might explain these observed benefits. We studied the number and function of EPC at baseline and after a cardio-pulmonary exercise test (CPET). METHODS: Endothelial function was assessed by flow mediated dilation (FMD) of the brachial artery in 41 sedentary CHF patients (pts). Twenty two pts were classified as mild CHF (62 ± 3 yrs, NT-proBNP < 800 pg/ml, LVEF 32 ± 1%, FMD 5.3 ± 0.5%, mean ± SEM) and 19 as severe CHF (63 ± 3 yrs, NT-proBNP > 800 pg/ml, LVEF 23 ± 2%, FMD 6.4 ± 0.6%). Circulating CD34+ and CD34+/KDR+ cells (EPC) were determined by flow cytometry before and 10 minutes after CPET. Migration of UEA+/acLDL+EPC towards VEGF and SDF-1a was assessed at day 7 of culture. Thirteen age-matched healthy subjects (56 ± 2 yrs, FMD 7.1 ± 0.4%) served as controls. RESULTS: Numbers of CD34+ cells were decreased in both mild (0.329 ± 0.07 of lymphocytes) and severe CHF pts (0.336 ± 0.05%) compared to healthy controls (0.599 ± 0.09%) and correlated positively with VO2 peak and maximal workload (all p<0.05). Numbers of CD34+/KDR+ cells were not significantly different between groups. Migratory capacity of EPC was significantly decreased in mild CHF pts (35.5 ± 3.1%) and severe CHF pts (33.1 ± 3.8%) compared to healthy subjects (63.7 ± 5.7%, p< 0.05) and correlated with VO2peak (r = 0.682, p = 0.021). Following exercise, migratory capacity improved acutely in mild CHF pts (35.5 ± 3.1% vs. 46.2 ± 3.5%, p = 0.005) and severe CHF pts (33.1 ± 3.8% vs. 50.1 ± 3.8%, p = 0.003), whereas a significant improvement was absent in healthy subjects (63.7 ± 5.6% vs. 52.4 ± 4.9%, p> 0.05). A single exercise bout had no effect on circulating EPC numbers. CONCLUSION: CHF patients exhibit reduced EPC numbers and function which is correlated to disease severity and exercise capacity. Acute exercise improves migratory activity of EPC, whereas their number remains unaltered. The increase is larger in advanced disease stages. The latter suggests that the exercise-induced stimulus for endothelial restoration is larger in clinically more affected patients. Supported by a grant from the Fund for Scientific Research, Vlaanderen
Published Version
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