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.