{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:30:15Z","timestamp":1783629015135,"version":"3.55.0"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Practical Research Project for Rare \/ Intractable Diseases from Japan Agency for Medical Research and Development","award":["20ek0109487h0001"],"award-info":[{"award-number":["20ek0109487h0001"]}]},{"name":"Practical Research Project for Rare \/ Intractable Diseases from Japan Agency for Medical Research and Development","award":["23ek0109560h0003"],"award-info":[{"award-number":["23ek0109560h0003"]}]},{"name":"Practical Research Project for Rare \/ Intractable Diseases from Japan Agency for Medical Research and Development","award":["23ek0109643h0001"],"award-info":[{"award-number":["23ek0109643h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:p>\n                    Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive narrowing of pulmonary arterioles. Although VEGF is highly expressed in lung of patients with PH and in animal PH models, the involvement of angiogenesis remains elusive. To clarify the pathophysiological function of angiogenesis in PH, we compared the angiogenic response in hypoxia (Hx) and SU5416 (a VEGFR2 inhibitor) plus Hx (SuHx) mouse PH models using 3D imaging. The 3D imaging analysis revealed an angiogenic response in the lung of the Hx-PH, but not of the severer SuHx-PH model. Selective VEGFR2 inhibition with cabozantinib plus Hx in mice also suppressed angiogenic response and exacerbated Hx-PH to the same extent as SuHx. Expression of endothelial proliferator-activated receptor \u03b3 coactivator 1\u03b1 (PGC-1\u03b1) increased along with angiogenesis in lung of Hx-PH but not SuHx mice. In pulmonary endothelial cell\u2013specific\n                    <jats:italic>Ppargc1a<\/jats:italic>\n                    -KO mice, the Hx-induced angiogenesis was suppressed, and PH was exacerbated along with increased oxidative stress, cellular senescence, and DNA damage. By contrast, treatment with baicalin, a flavonoid enhancing PGC-1\u03b1 activity in endothelial cells, ameliorated Hx-PH with increased\n                    <jats:italic>Vegfa<\/jats:italic>\n                    expression and angiogenesis. Pulmonary endothelial PGC-1\u03b1\u2013mediated angiogenesis is essential for adaptive responses to Hx and might represent a potential therapeutic target for PH.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.162632","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T14:00:46Z","timestamp":1694095246000},"source":"Crossref","is-referenced-by-count":18,"title":["PGC-1\u03b1\u2013mediated angiogenesis prevents pulmonary hypertension in mice"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-3997","authenticated-orcid":true,"given":"Takayuki","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan."},{"name":"Department of Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan."},{"name":"Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-3347","authenticated-orcid":true,"given":"Norifumi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan."},{"name":"Department of Advanced Translational Research and Medicine in Management of Pulmonary Hypertension, The University of Tokyo, Bunkyo-ku, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, 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