Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis.
BACKGROUND
The molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to exert beneficial effects on atherosclerosis, angiogenesis, and vascular repair.


RESULTS
To study the effect of physical activity on the bone marrow, EPCs were quantified by fluorescence-activated cell sorter analysis in mice randomized to running wheels (5.1+/-0.8 km/d, n=12 to 16 per group) or no running wheel. Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267+/-19%, 289+/-22%, and 280+/-25% of control levels after 7, 14, and 28 days, respectively, accompanied by a similar increase of EPCs in the bone marrow and EPCs expanded from spleen-derived mononuclear cells. eNOS-/- mice and wild-type mice treated with N(G)-nitro-l-arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity. Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs. Running inhibited neointima formation after carotid artery injury by 22+/-2%. Neoangiogenesis, as assessed in a subcutaneous disc model, was increased by 41+/-16% compared with controls. In patients with stable coronary artery disease (n=19), moderate exercise training for 28 days led to a significant increase in circulating EPCs and reduced EPC apoptosis.


CONCLUSIONS
Physical activity increases the production and circulating numbers of EPCs via a partially NO-dependent, antiapoptotic effect that could potentially underlie exercise-related beneficial effects on cardiovascular diseases.
Laufs
Ulrich
U
Medizinische Klinik und Poliklinik der Universität des Saarlandes, Innere Medizin III, Homburg, Germany. ulrich@laufs.com
Werner
Nikos
N
Link
Andreas
A
Endres
Matthias
M
Wassmann
Sven
S
Jürgens
Kristina
K
Miche
Eckart
E
Böhm
Michael
M
Nickenig
Georg
G
D000368:Aged; D000818:Animals; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000628:therapy; D004730:Endothelium, Vascular / Q000166:cytology*; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010805:Physical Conditioning, Animal; D013234:Stem Cells / Q000166:cytology*; D017539:Tunica Intima / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse