title: Cooperation between VEGF and beta3 integrin during cardiac vascular development.
abstract: In the developing myocardium, vascular endothelial growth factor (VEGF)-dependent neovascularization occurs by division of existing vessels, a process that persists for several weeks following birth. During this remodeling phase, mRNA expression of beta3 integrin in the heart decreases significantly as vessel maturation progresses. However, in male mice lacking beta3, coronary capillaries fail to mature and continue to exhibit irregular endothelial thickness, endothelial protrusions into the lumen, and expanded cytoplasmic vacuoles. Surprisingly, this phenotype was not seen in female beta3-null mice. Enhanced VEGF signaling contributes to the beta3-null phenotype, because these vessels can be normalized by inhibitors of VEGF or Flk-1. Moreover, intravenous injection of VEGF induces a similar angiogenic phenotype in hearts of adult wild-type mice. These findings show a clear vascular phenotype in the hearts of mice lacking beta3 and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF.
authors.affiliation: Moores UCSD Cancer Center, University of California, San Diego, CA 92093-0803, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Weis
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Lindquist
authors.forename: Leo A
authors.initials: LA
authors.lastname: Barnes
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Lutu-Fuga
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cui
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Wood
authors.forename: David A
authors.initials: DA
authors.lastname: Cheresh
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2