Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke.
The purpose of this study was to determine if exercise could induce expression of vascular endothelial growth factor (VEGF) and angiopoietin 1 and 2, in association with angiogenesis; and if angiogenic changes correlated with reduced brain injury in stroke. Adult male Sprague Dawley rats (3 month old, n=44) were exercised on a treadmill 30 minutes each day for 1, 3 or 6 weeks, or housed as non-exercised controls for 3 weeks. Some 3 week-exercised rats were then housed for an additional 3 weeks. Exercise significantly (p<0.01) increased mRNA (determined by real-time reverse transcriptase-polymerase chain reaction) expression of angiopoietin 1 and 2 as early as 1 week, with further increases occurring at 3 weeks. A mild increase after 1 week and a robust increase after 3 weeks of exercise in four isoforms (120, 144, 164, 188) of VEGF mRNA levels were significantly (p<0.01) observed, with VEGF(144) being more markedly up-regulated. Overexpression of the mRNAs decreased upon withdrawal of exercise. A significant increase (p<0.01) in the density of microvessels (determined by laminin-immunocytochemistry) was found at 3 weeks of exercise and this continued after exercise was withdrawn. In exercising rats subjected to 2-h MCA occlusion followed by 48-h reperfusion, neurological deficits and infarct volume were significantly reduced. Neuroprotection continued after 3 weeks of rest. This study indicates that pre-ischemic exercise reduces brain injury in stroke. The reduced damage is associated with angiogenesis, possibly induced by angiogenic factors following exercise. Physical exercise up-regulates mRNA levels of the angiopoietin family and VEGF.
Ding
Yun-Hong
YH
Department of Neurologicalal Surgery, Wayne State University School of Medicine, Lande Medical Research Building, Room 48, 550 E. Canfield Street, Detroit, MI 48201, USA. yding@med.wayne.edu
Luan
Xia-Dong
XD
Li
Jie
J
Rafols
José A
JA
Guthinkonda
M
M
Diaz
Fernando G
FG
Ding
Yuchuan
Y
D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry / Q000295:instrumentation; D007797:Laminin / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D009460:Neurologic Examination / Q000379:methods; D010805:Physical Conditioning, Animal / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000534:rehabilitation*; D020521:Stroke / Q000150:complications / Q000378:metabolism*; D000071939:Stroke Rehabilitation; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D007797:Laminin; D042461:Vascular Endothelial Growth Factor A