Hypoxia and physical activity improve angiogenesis, i.e. the formation of new from already existing blood vessels as well as the repair of already existing vessels by activating circulating endothelial progenitor cells. In the present study, we investigated whether preconditioned plasma samples obtained from men (age 232 years), who once performed a maximal exercise cycling testing (100 W, + 30W every min until exhaustion) under simulated normobaric hypoxic conditions (4000 m), influences apoptosis (immunohistochemical detection of activated caspase), proliferation (immunohistochemical detection of ki67) and senescence (ß-galactosidase assay) of endothelial progenitor cells (EPC). EPC were isolated from buffy coat preparations (normoxia, no physical activity). Plasma samples were taken directly before, 10 minutes, and 4 hours after the altitude training. In addition, we measured the release of classical angiogenetic activators (VEGF (angiogenesis-inductor), endostatin (angiogenesis inhibitor) and erythropoietin (EPC-mobilisator) by ELISA technique. The one time cycling exercise training, which was performed under normobaric hypoxic conditions, did not alter plasma concentrations of VEGF, endostatin or erythropoietin. If being incubated with the plasma obtained under hypoxic exercising conditions, no alterations were observed regarding proliferation or apoptosis of EPC. Interestingly, a significant decrease in EPC-senescence was observed 10 min as well as 4 hours after the hypoxic exercise testing (EPC-senescence (%), before: 1.90.4; after 10 min 0.70.5; after 4 h 0.70.4). In addition, we investigated senescence in EPC obtained from high performance athletes before and after a training camp under high altitude conditions (Flagstaff, USA, 2400 m) or under n.n. (Rügen, Germany) conditions. EPC senescence was significantly increased after the training camp, however this increase much more pronounced in the high altitude Flagstaff group compared to the N.N. group (EPC senescence (%): N.N., before: 5.51.2% vs. after 12.52.0%; Flagstaff, before: 2.72.1% after 47.5 4.3%).

Conclusion: 

The present studies indicate that already a short time stay under hypoxic conditions induces plasma alterations which decrease EPC senescence. These alterations are independent from the classical angiogenesis modulating factors VEGF, endostatin and erythropoietin. Chronic hypoxic conditions however increase cellular senescence.