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Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia.
Vasc Med. 2009 Feb; 14(1):29-36.VM

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 beta-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 beta-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.

Authors+Show Affiliations

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19144777

Citation

Ruifrok, Willem-Peter T., et al. "Estradiol-induced, Endothelial Progenitor Cell-mediated Neovascularization in Male Mice With Hind-limb Ischemia." Vascular Medicine (London, England), vol. 14, no. 1, 2009, pp. 29-36.
Ruifrok WP, de Boer RA, Iwakura A, et al. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia. Vasc Med. 2009;14(1):29-36.
Ruifrok, W. P., de Boer, R. A., Iwakura, A., Silver, M., Kusano, K., Tio, R. A., & Losordo, D. W. (2009). Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia. Vascular Medicine (London, England), 14(1), 29-36. https://doi.org/10.1177/1358863X08096666
Ruifrok WP, et al. Estradiol-induced, Endothelial Progenitor Cell-mediated Neovascularization in Male Mice With Hind-limb Ischemia. Vasc Med. 2009;14(1):29-36. PubMed PMID: 19144777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia. AU - Ruifrok,Willem-Peter T, AU - de Boer,Rudolf A, AU - Iwakura,Atsushi, AU - Silver,Marcy, AU - Kusano,Kengo, AU - Tio,Rene A, AU - Losordo,Douglas W, PY - 2009/1/16/entrez PY - 2009/1/16/pubmed PY - 2009/4/25/medline SP - 29 EP - 36 JF - Vascular medicine (London, England) JO - Vasc Med VL - 14 IS - 1 N2 - 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 beta-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 beta-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. SN - 1358-863X UR - https://www.unboundmedicine.com/medline/citation/19144777/Estradiol_induced_endothelial_progenitor_cell_mediated_neovascularization_in_male_mice_with_hind_limb_ischemia_ L2 - https://journals.sagepub.com/doi/10.1177/1358863X08096666?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -