{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:28:56Z","timestamp":1790702936615,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kees Westermann Fonds, stichting wetenschappelijk onderzoek Rendu Osler (SWORO)","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this review, we discuss the role of transforming growth factor-beta (TGF-\u03b2) in the development of pulmonary vascular disease (PVD), both pulmonary arteriovenous malformations (AVM) and pulmonary hypertension (PH), in hereditary hemorrhagic telangiectasia (HHT). HHT or Rendu-Osler-Weber disease is an autosomal dominant genetic disorder with an estimated prevalence of 1 in 5000 persons and characterized by epistaxis, telangiectasia and AVMs in more than 80% of cases, HHT is caused by a mutation in the ENG gene on chromosome 9 encoding for the protein endoglin or activin receptor-like kinase 1 (ACVRL1) gene on chromosome 12 encoding for the protein ALK-1, resulting in HHT type 1 or HHT type 2, respectively. A third disease-causing mutation has been found in the SMAD-4 gene, causing a combination of HHT and juvenile polyposis coli. All three genes play a role in the TGF-\u03b2 signaling pathway that is essential in angiogenesis where it plays a pivotal role in neoangiogenesis, vessel maturation and stabilization. PH is characterized by elevated mean pulmonary arterial pressure caused by a variety of different underlying pathologies. HHT carries an additional increased risk of PH because of high cardiac output as a result of anemia and shunting through hepatic AVMs, or development of pulmonary arterial hypertension due to interference of the TGF-\u03b2 pathway. HHT in combination with PH is associated with a worse prognosis due to right-sided cardiac failure. The treatment of PVD in HHT includes medical or interventional therapy.<\/jats:p>","DOI":"10.3390\/ijms22073471","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"3471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Pulmonary Vascular Complications in Hereditary Hemorrhagic Telangiectasia and the Underlying Pathophysiology"],"prefix":"10.3390","volume":"22","author":[{"given":"Sala","family":"Bofarid","sequence":"first","affiliation":[{"name":"Department of Cardiology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Hosman","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes J.","family":"Mager","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Repke J.","family":"Snijder","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco C.","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"},{"name":"Department of Cardiology, University Medical Center Utrecht, 3584 CM Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/humu.10026","article-title":"Genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan","volume":"19","author":"Dakeishi","year":"2002","journal-title":"Hum. 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