Protective role of COMP-Ang1 in ischemic rat brain.
In cerebral ischemia, the induction of angiogenesis may represent a natural defense mechanism that enables the hypoxic brain to avoid progression into infarction. Angiopoietin-1 (Ang1) is known to produce non-leaky and stable blood vessel formation mainly by the Tie2 receptor. Therefore, we envisioned that the application of cartilage oligomeric matrix protein-Ang1 (COMP-Ang1), a soluble, stable, and potent form of Ang1, would promote angiogenesis and provide a protective effect following unilateral middle cerebral artery occlusion (MCAO) in rats. To this end, we employed a 2-hour-MCAO model, and treated rats with adenovirus encoding COMP-Ang1 (Ade-COMP-Ang1) or control virus encoding beta-gal (Ade-beta-gal). Time course magnetic resonance images (MRIs) revealed significantly reduced infarct volume in the rats treated with Ade-COMP-Ang1 with an improvement of post-ischemic neurological deficits compared with rats treated with Ade-beta-gal. Moreover, compared to the rats treated with Ade-beta-gal, the rats treated with Ade-COMP-Ang1 showed an increase in blood vessels, especially in the border zone adjacent to the infarction, increased number of endogenous neuronal progenitor cells in the ischemic brain, and decreased number of TUNEL-positive cells. Taken together, COMP-Ang1 reduced infarct volume and consequently attenuated post-ischemic neurological deficits through enhanced angiogenesis and increased viable cell mass of neuronal cells.
Shin
Hye Young
HY
Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.
Lee
Yoon Jin
YJ
Kim
Hak Joo
HJ
Park
Chul-Kee
CK
Kim
Jong Hoon
JH
Wang
Kyu Chang
KC
Kim
Dong Gyu
DG
Koh
Gou Young
GY
Paek
Sun Ha
SH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000502:physiology; D019610:Cytoprotection / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000627:therapeutic use*; D020127:Recovery of Function / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
C515576:COMP-Ang1 fusion protein; D011993:Recombinant Fusion Proteins