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The ensuing unique hemodynamic conditions compromise the endothelial function both in the pulmonary and the systemic circulation. The underlying pathophysiological mechanisms, although distinct within each vascular bed, are interrelated and may collectively contribute to progressive end-organ dysfunction, ultimately accounting for the significant morbidity burden in Fontan patients. This review provides an overview of the current knowledge on the pathophysiology of pulmonary and systemic vasculopathy in Fontan circulation, with particular emphasis on the interplay between endothelial dysfunction and adverse clinical outcomes. Remaining gaps in knowledge and directions of future research are also discussed.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s10456-025-09996-2","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T15:28:22Z","timestamp":1755790102000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathophysiology of endothelial dysfunction in Fontan circulation: from bench to bedside and back again"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-8259","authenticated-orcid":false,"given":"Amalia","family":"Baroutidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7054-1422","authenticated-orcid":false,"given":"Artemios G.","family":"Karagiannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-1642","authenticated-orcid":false,"given":"Theodoros","family":"Dimitroulas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Kamperidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Ziakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Dimopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7491-6319","authenticated-orcid":false,"given":"George","family":"Giannakoulas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"9996_CR1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1161\/CIRCULATIONAHA.105.592378","volume":"115","author":"P Khairy","year":"2007","unstructured":"Khairy P, Poirier N, Mercier L-A (2007) Univentricular heart. 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