{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:30Z","timestamp":1791908250442,"version":"4.3.4"},"reference-count":34,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Brain derived neurotrophic factor, BDNF, is a neurotrophin best characterized for its survival and differentiative effects on neurons expressing the trk B receptor tyrosine kinase. Although many of these neurons are lost in the BDNF\u2212\/\u2212 mouse, the early postnatal lethality of these animals suggests a wider function for this growth factor. Here, we demonstrate that deficient expression of BDNF impairs the survival of endothelial cells in intramyocardial arteries and capillaries in the early postnatal period, although the embryonic vasculature can remodel into arteries, capillaries and veins. BDNF deficiency results in a reduction in endothelial cell-cell contacts and in endothelial cell apoptosis, leading to intraventricular wall hemorrhage, depressed cardiac contractility and early postnatal death. Vascular hemorrhage is restricted to cardiac vessels, reflecting the localized expression of BDNF and trk B by capillaries and arterioles in this vascular bed. Conversely, ectopic BDNF overexpression in midgestational mouse hearts results in an increase in capillary density. Moreover, BDNF activation of endogenous trk B receptors supports the survival of cardiac microvascular endothelial cells cultured from neonatal mice. These results establish an essential role for BDNF in maintaining vessel stability in the heart through direct angiogenic actions on endothelial cells.<\/jats:p>","DOI":"10.1242\/dev.127.21.4531","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:21:24Z","timestamp":1619410884000},"page":"4531-4540","source":"Crossref","is-referenced-by-count":364,"title":["Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization"],"prefix":"10.1242","volume":"127","author":[{"given":"Michael J.","family":"Donovan","sequence":"first","affiliation":[{"name":"1 Millennium Pharmaceuticals, Cambridge, and the Department of Pathology, Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle I.","family":"Lin","sequence":"additional","affiliation":[{"name":"2 Department of Medicine and Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phi","family":"Wiegn","sequence":"additional","affiliation":[{"name":"2 Department of Medicine and Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ringstedt","sequence":"additional","affiliation":[{"name":"4 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Kraemer","sequence":"additional","affiliation":[{"name":"3 Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hahn","sequence":"additional","affiliation":[{"name":"2 Department of Medicine and Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"3 Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F.","family":"Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"4 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Rafii","sequence":"additional","affiliation":[{"name":"2 Department of Medicine and Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara L.","family":"Hempstead","sequence":"additional","affiliation":[{"name":"2 Department of Medicine and Weill Medical College of Cornell University, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"2023030307380917100_","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1126\/science.284.5415.808","article-title":"Effects of angiogenesis inhibitors on multistage carcinogenesis in mice","volume":"284","author":"Bergers","year":"1999","journal-title":"Science"},{"key":"2023030307380917100_","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0092-8674(00)81010-7","article-title":"Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial cell survival and angiogenesis","volume":"23","author":"Carmeliet","year":"1999","journal-title":"Cell"},{"key":"2023030307380917100_","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and srteriogenesis","volume":"6","author":"Carmeliet","year":"2000","journal-title":"Nature Med"},{"key":"2023030307380917100_","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0166-2236(95)93922-K","article-title":"p75 and trk: a two receptor system","volume":"18","author":"Chao","year":"1995","journal-title":"Trends Neurosci"},{"key":"2023030307380917100_","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1172\/JCI6127","article-title":"Blood vessel maturation: vascular development comes of age","volume":"103","author":"Darland","year":"1999","journal-title":"J. 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