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- Title
Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia.
- Authors
Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.
- Abstract
We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and implanted with placebo pellets or pellets containing low-dose estradiol (0.39 mg) or high-dose estradiol (1.7 mg). Hind-limb ischemia was induced by unilateral resection of the left femoral artery 1 week after pellet implantation, then EPC mobilization and functional recovery was evaluated. EPC recruitment was assessed in mice transplanted with bone marrow from transgenic donors expressing β-galactosidase driven by the Tie-2 promoter. EPC culture assay performed 2 weeks after pellet implantation revealed a significantly greater (p < 0.05) number of circulating EPCs in the high-dose estradiol group than in the low-dose estradiol and placebo groups. At 3 and 4 weeks after induction of hind-limb ischemia, perfusion was significantly greater (p < 0.05) in high-dose estradiol mice than in mice implanted with the low-dose estradiol or placebo pellets. At 1 and 4 weeks after hind-limb ischemia surgery, more bone marrow-derived EPCs, identified as β-galactosidase-positive cells, were observed in ischemic regions from high-dose estradiol animals than in low-dose (p < 0.05) or placebo groups (p < 0.05). These results indicate that estradiol dose-dependently increases the levels of EPCs in peripheral blood in male animals, improves the recovery of blood flow, and decreases limb necrosis after hind-limb ischemia, and that this enhancement occurs, in part, through augmentation of EPC mobilization and greater incorporation of bone marrow-derived EPCs into foci of neovascularization.
- Subjects
NEOVASCULARIZATION; VASCULAR endothelial growth factors; ESTRADIOL; ISCHEMIA; BLOOD flow; BLOOD circulation; LABORATORY mice
- Publication
Vascular Medicine, 2009, Vol 14, Issue 1, p29
- ISSN
1358-863X
- Publication type
Article
- DOI
10.1177/1358863X08096666