Estrogen deficiency attenuates neovascularization in a murine model of hindlimb ischemia.
BACKGROUND
The possible relation between menopause and the development of peripheral arterial disease, especially lower extremity disease, has not been fully studied. To explore this issue, we investigated whether estrogen deficiency affected neovascularization in a murine model of hindlimb ischemia.


METHODS
Ischemia was surgically induced in one hindlimb of oophorectomized and control female BALB/c mice. Neovascularization in the ischemic hindlimbs was evaluated using laser Doppler blood flow analysis and capillary density analysis of the adductor muscle. The expression of endothelial nitric oxide synthase protein in the adductor muscle of the ischemic hindlimbs was assessed.


RESULTS
The plasma 17-β estradiol levels were significantly lower in the oophorectomized mice than in the control mice. The oophorectomized mice also had a significantly reduced blood perfusion index and capillary density on day 21 after the induction of hindlimb ischemia and significant suppression of endothelial nitric oxide synthase protein expression on day 3 after ischemia induction.


CONCLUSIONS
Estrogen deficiency attenuated neovascularization in a murine model of hindlimb ischemia. Impaired neovascularization in oophorectomized mice might correlate with a reduction in endothelial nitric oxide synthase expression caused by estrogen deficiency.
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Kentaro
K
Matsubara
Hirohisa
H
Harada
Nobutoshi
N
Ando
Susumu
S
Watada
Hideaki
H
Obara
Kenji
K
Matsumoto
Yuko
Y
Kitagawa
D000818:Animals; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D058729:Peripheral Arterial Disease / Q000209:etiology
D004967:Estrogens; D009569:Nitric Oxide; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III