{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:58:12Z","timestamp":1787497092750,"version":"build-2736575974"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,8,30]]},"abstract":"<jats:p>\n                    Oxidative stress exacerbates neovascularization (NV) in many disease processes. In this study we investigated the mechanism of that effect. Mice deficient in superoxide dismutase 1 (\n                    <jats:italic>\n                      Sod1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice) have increased oxidative stress and show severe ocular NV that is reduced to baseline by antioxidants. Compared with wild-type mice with ischemic retinopathy,\n                    <jats:italic>\n                      Sod1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice with ischemic retinopathy had increased expression of several NF-\u03baB\u2013responsive genes, but expression of\n                    <jats:italic>vascular cell-adhesion molecule-1<\/jats:italic>\n                    (\n                    <jats:italic>Vcam1<\/jats:italic>\n                    ) was particularly high. Intraocular injection of anti\u2013VCAM-1 antibody eliminated the excessive ischemia-induced retinal NV. Elements that contributed to oxidative stress-induced worsening of retinal NV that were abrogated by blockade of VCAM-1 included increases in leukostasis, influx of bone marrow-derived cells, and capillary closure. Compared with ischemia alone, ischemia plus oxidative stress resulted in increased expression of several HIF-1\u2013responsive genes caused in part by VCAM-1\u2013induced worsening of nonperfusion and, hence, ischemia, because anti\u2013VCAM-1 significantly reduced the increased expression of all but one of the genes. These data explain why oxidative stress worsens ischemia-induced retinal NV and may be relevant to other neovascular diseases in which oxidative stress has been implicated. The data also suggest that antagonism of VCAM-1 provides a potential therapy to combat worsening of neovascular diseases by oxidative stress.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1012859108","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T04:34:54Z","timestamp":1313469294000},"page":"14614-14619","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Vascular cell-adhesion molecule-1 plays a central role in the proangiogenic effects of oxidative stress"],"prefix":"10.1073","volume":"108","author":[{"given":"Aling","family":"Dong","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikui","family":"Shen","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MingBing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,8,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.4.1474"},{"key":"e_1_3_3_2_2","first-page":"182","article-title":"Hypoxia inducible factor-1\u03b1 is increased in ischemic retina: Temporal and spatial correlation with VEGF expression","volume":"40","author":"Ozaki H","year":"1999","unstructured":"H Ozaki, et al., Hypoxia inducible factor-1\u03b1 is increased in ischemic retina: Temporal and spatial correlation with VEGF expression. 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