{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:08:31Z","timestamp":1791295711073,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2003,12,23]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            We hypothesized that estrogen-induced acceleration of reendothelialization might be mediated in part by effects involving mobilization and incorporation of bone marrow\u2013derived endothelial progenitor cells (EPCs).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Carotid injury was induced in ovariectomized wild-type mice receiving either 17\u03b2-estradiol or placebo. Estradiol treatment significantly accelerated reendothelialization of injured arterial segments within 7 days and resulted in a significant reduction of medial thickness 14 and 21 days after the injury. Significant increases in circulating EPCs 3 days after the injury were observed in the estradiol group compared with placebo-treated mice. These data were further supported by fluorescence-activated cell sorting analysis, which disclosed a significant increase in Sca-1\/Flk-1\u2013positive cells in estradiol versus control mice. To evaluate the effects of estradiol on bone marrow\u2013derived EPC incorporation at sites of reendothelialization, carotid injury was established in ovariectomized wild-type mice transplanted with bone marrow from transgenic donors expressing \u03b2-galactosidase transcriptionally regulated by the Tie-2 promoter. Significantly greater numbers of X-gal\u2013positive cells were observed at reendothelialized areas in the estradiol group 3 days after injury as compared with placebo. Fluorescent immunohistochemistry 14 days after the injury documented a marked increase in cells expressing both \u03b2-gal, indicating bone marrow origin and Tie-2 expression, and isolectin B4, also indicating endothelial lineage, in the estradiol group compared with control. In contrast, estradiol did not accelerate reendothelialization or augment EPC mobilization into the peripheral circulation after injury in endothelial nitric oxide synthase\u2013deficient mice (eNOS\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ). Furthermore, estradiol exhibited direct stimulatory effects on EPC mitogenic and migration activity and inhibited EPC apoptosis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Estradiol accelerates reendothelialization and attenuates medial thickening after carotid injury in part by augmenting mobilization and proliferation of bone marrow\u2013derived EPCs and their incorporation into the recovering endothelium at the site of injury.\n          <\/jats:p>","DOI":"10.1161\/01.cir.0000106906.56972.83","type":"journal-article","created":{"date-parts":[[2003,12,16]],"date-time":"2003-12-16T01:25:09Z","timestamp":1071537909000},"page":"3115-3121","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":352,"title":["Estrogen-Mediated, Endothelial Nitric Oxide Synthase\u2013Dependent Mobilization of Bone Marrow\u2013Derived Endothelial Progenitor Cells Contributes to Reendothelialization After Arterial Injury"],"prefix":"10.1161","volume":"108","author":[{"given":"Atsushi","family":"Iwakura","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Luedemann","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubha","family":"Shastry","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Hanley","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Kearney","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Aikawa","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Isner","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Asahara","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas W.","family":"Losordo","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Research, St Elizabeth\u2019s Medical Center, Tufts University School of Medicine, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","first-page":"985","volume":"143","year":"1993","journal-title":"Am J 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