title: Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains.
abstract: Angiogenesis is a critical element for adaptation to low levels of oxygen and occurs following long-term exposure to mild hypoxia in rats. To test whether a similar response in mice occurs, CD1, 129/Sv, C57Bl/6, and Balb/c mice were exposed to 10% oxygen for up to 3 wk. All mice showed significant increases in the percentage of packed red blood cells, and CD1 and 129/Sv mice showed increased respiration frequency and minute volume, common physiological measures of hypoxia. Significant angiogenesis was observed in all strains except Balb/c following 3-wk exposure to chronic hypoxia. CD1 hypoxic mice had the largest increase (88%), followed by C57Bl/6 (48%), 129/Sv (41%), and Balb/c (12%), suggesting that some mice undergo more remodeling than others in response to hypoxia. Protein expression analysis of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang2, and Tie2 were examined to determine whether regulation of different angiogenic proteins could account for the differences observed in hypoxia-induced angiogenesis. CD1 mice showed the strongest upregulation of VEGF, Ang2, Ang1, and Tie2, whereas Balb/c had only subtle increases in VEGF and no change in the other proteins. C57Bl/6 mice showed a regulatory response that fell between the CD1 and Balb/c mice, consistent with the intermediate increase in angiogenesis. Our results suggest that genetic heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins and needs to be accounted for when designing and interpreting experiments using transgenic mice and when studying in vivo models of angiogenesis.
authors.affiliation: Dept. of Dermatology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. nicole.ward@case.edu
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moore
authors.forename: Kristen
authors.initials: K
authors.lastname: Noon
authors.forename: Nicholas
authors.initials: N
authors.lastname: Spassil
authors.forename: Erica
authors.initials: E
authors.lastname: Keenan
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Ivanco
authors.forename: Joseph C
authors.initials: JC
authors.lastname: LaManna
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D042501:Angiogenic Proteins / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000031:analogs & derivatives / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D014644:Genetic Variation; D006400:Hematocrit; D000860:Hypoxia / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D042787:Receptor, TIE-2 / Q000378:metabolism; D015656:Respiratory Mechanics; D013045:Species Specificity; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D042787:Receptor, TIE-2