title: Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia.
abstract: Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer α-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.
authors.affiliation: Cardiovascular Research Institute, MedStar Health Research Institute, 108 Irving St., NW, Rm. 214, Washington, DC 20010, USA.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Peng
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Lassance-Soares
authors.forename: Amir H
authors.initials: AH
authors.lastname: Najafi
authors.forename: Subeena
authors.initials: S
authors.lastname: Sood
authors.forename: Nima
authors.initials: N
authors.lastname: Aghili
authors.forename: Lee O
authors.initials: LO
authors.lastname: Alderman
authors.forename: Julio A
authors.initials: JA
authors.lastname: Panza
authors.forename: James E
authors.initials: JE
authors.lastname: Faber
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
mesh_terms: D000818:Animals; D005260:Female; D005263:Femoral Artery / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism; D007511:Ischemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology*; D012727:Sex Characteristics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III