title: Contrasting roles of E2F2 and E2F3 in endothelial cell growth and ischemic angiogenesis.
abstract: The growth of new blood vessels after ischemic injury requires endothelial cells (ECs) to divide and proliferate, and the E2F transcription factors are key regulators of the genes responsible for cell-cycle progression; however, the specific roles of individual E2Fs in ECs are largely unknown. To determine the roles of E2F2 and E2F3 in EC proliferation and the angiogenic response to ischemic injury, hind-limb ischemia was surgically induced in E2F2(-/-) mice, endothelial-specific E2F3-knockout (EndoE2F3(∆/∆)) mice, and their littermates with wild-type E2F2 and E2F3 expression. Two weeks later, Laser-Doppler perfusion measurements, capillary density, and endothelial proliferation were significantly greater in E2F2(-/-) mice and significantly lower in EndoE2F3(∆/∆) mice than in their littermates, and EndoE2F3(∆/∆) mice also developed toe and limb necrosis. The loss of E2F2 expression was associated with increases in the proliferation and G1/S-phase gene expression of isolated ECs, while the loss of E2F3 expression led to declines in these parameters. Thus E2F2 impairs, and endothelial E2F3 promotes, the angiogenic response to peripheral ischemic injury through corresponding changes in EC cell-cycle progression.
authors.affiliation: Feinberg Cardiovascular Research Institute, Department of Medicine-Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Chan
authors.initials: C
authors.lastname: Boriboun
authors.forename: Kentaro
authors.initials: K
authors.lastname: Jujo
authors.forename: Shiyue
authors.initials: S
authors.lastname: Xu
authors.forename: Ting C
authors.initials: TC
authors.lastname: Zhao
authors.forename: Yao-Liang
authors.initials: YL
authors.lastname: Tang
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
mesh_terms: D000818:Animals; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D016193:G1 Phase; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016196:S Phase
chemical_list: D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; C484940:E2f2 protein, mouse; C490840:E2f3 protein, mouse