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Although dysregulation of angiogenic mediators has been implicated in pulmonary fibrosis, the specific rate\u2010limiting angiogenic markers involved and their role in the progression of pulmonary fibrosis remains unclear. We demonstrate that bleomycin treatment induces angiogenesis, and inhibition of the central angiogenic mediator VEGF using anti\u2010VEGF antibody CBO\u2010P11 significantly attenuates bleomycin\u2010induced pulmonary fibrosis in vivo. Bleomycin\u2010induced nitric oxide (NO) was observed to be the key upstream regulator of VEGF via the PI3k\/Akt pathway. VEGF regulated other important angiogenic proteins including PAI\u20101 and IL\u20108 in response to bleomycin exposure. Inhibition of NO and VEGF activity significantly mitigated bleomycin\u2010induced angiogenic and fibrogenic responses. NO and VEGF are key mediators of bleomycin\u2010induced pulmonary fibrosis, and could serve as important targets against this debilitating disease. Overall, our data suggests an important role for angiogenic mediators in the pathogenesis of bleomycin\u2010induced pulmonary fibrosis. J. Cell. Biochem. 116: 2484\u20132493, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25192","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T11:25:33Z","timestamp":1430220333000},"page":"2484-2493","source":"Crossref","is-referenced-by-count":61,"title":["Nitric Oxide Mediates Bleomycin\u2010induced Angiogenesis and Pulmonary Fibrosis via Regulation of VEGF"],"prefix":"10.1002","volume":"116","author":[{"given":"Anand Krishnan V.","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vani","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School Norfolk Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Castro","sequence":"additional","affiliation":[{"name":"Magee Women's Research Institute University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Kaushik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh M.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton A.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajkumar","family":"Venkatadri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon","family":"Rojanasakul","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences West Virginia University Morgantown West Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy, Hampton University Hampton Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.41.4.467"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602551200"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.03.022"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm763"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","unstructured":"CarmelietP CollenD.2000. y of Sciences. 902:249\u2010262; discussion 262\u2010244.Molecular basis of angiogenesis. 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