{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:43:19Z","timestamp":1790649799526,"version":"4.1.0"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2020,1,17]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>\n                      ENG (endoglin) is a coreceptor for BMP (bone morphogenetic protein) 9\/10 and is strongly expressed in endothelial cells. Mutations in\n                      <jats:italic>ENG<\/jats:italic>\n                      lead to the inherited vascular disorder hereditary hemorrhagic telangiectasia characterized by local telangiectases and larger arteriovenous malformations (AVMs); but how ENG functions to regulate the adult vasculature is not understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The goal of the work was to determine how ENG maintains vessel caliber in adult life to prevent AVM formation and thereby protect heart function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      Genetic depletion of endothelial\n                      <jats:italic>Eng<\/jats:italic>\n                      in adult mice led to a significant reduction in mean aortic blood pressure. There was no evidence of hemorrhage, anemia, or AVMs in major organs to explain the reduced aortic pressure. However, large AVMs developed in the peripheral vasculature intimately associated with the pelvic cartilaginous symphysis\u2014a noncapsulated cartilage with a naturally high endogenous expression of VEGF (vascular endothelial growth factor). The increased blood flow through these peripheral AVMs explained the drop in aortic blood pressure and led to increased cardiac preload, and high stroke volumes, ultimately resulting in high-output heart failure. Development of pelvic AVMs in this region of high VEGF expression occurred because loss of ENG in endothelial cells leads to increased sensitivity to VEGF and a hyperproliferative response. Development of AVMs and associated progression to high-output heart failure in the absence of endothelial ENG was attenuated by targeting VEGF signaling with an anti-VEGFR2 (VEGF receptor 2) antibody.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>ENG promotes the normal balance of VEGF signaling in quiescent endothelial cells to maintain vessel caliber\u2014an essential function in conditions of increased VEGF expression such as local hypoxia or inflammation. In the absence of endothelial ENG, increased sensitivity to VEGF drives abnormal endothelial proliferation in local regions of high VEGF expression, leading to AVM formation and a rapid injurious impact on heart function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.119.315974","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T05:02:03Z","timestamp":1575608523000},"page":"243-257","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Loss of Endothelial Endoglin Promotes High-Output Heart Failure Through Peripheral Arteriovenous Shunting Driven by VEGF Signaling"],"prefix":"10.1161","volume":"126","author":[{"given":"Simon","family":"Tual-Chalot","sequence":"first","affiliation":[{"name":"From the Biosciences Institute (S.T.-C., R.E.R., E.S., B.D., C.P., H.L., H.M.A.), Faculty of Medical Sciences, Newcastle University, United 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