{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:59:33Z","timestamp":1779119973723,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000222","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["T5598"],"award-info":[{"award-number":["T5598"]}],"id":[{"id":"10.13039\/501100000222","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia caused by mutations in endoglin (<jats:italic>ENG<\/jats:italic>; HHT1) or activin receptor-like kinase (<jats:italic>ALK1<\/jats:italic>; HHT2) genes, coding for transforming growth factor-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>\u03b2<\/mml:mi><\/mml:mrow><\/mml:math>(TGF-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>\u03b2<\/mml:mi><\/mml:mrow><\/mml:math>) superfamily receptors. We demonstrated previously that endoglin and ALK1 interact with endothelial NO synthase (eNOS) and affect its activation. Endothelial cells deficient in endoglin or ALK1 proteins show eNOS uncoupling, reduced NO, and increased reactive oxygen species (ROS) production. In this study, we measured NO and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>levels in several organs of adult<jats:italic>Eng<\/jats:italic>and<jats:italic>Alk1<\/jats:italic>heterozygous mice, to ascertain whether decreased NO and increased ROS production is a generalized manifestation of HHT. A significant reduction in NO and increase in ROS production were found in several organs, known to be affected in patients. ROS overproduction in mutant mice was attributed to eNOS, as it was L-NAME inhibitable. Mitochondrial ROS contribution, blocked by antimycin, was highest in liver while NADPH oxidase, inhibited by apocynin, was a major source of ROS in the other tissues. However, there was no difference in antimycin- and apocynin-inhibitable ROS production between mutant and control mice. Our results indicate that eNOS-derived ROS contributes to endothelial dysfunction and likely predisposes to disease manifestations in several organs of HHT patients.<\/jats:p>","DOI":"10.1155\/2012\/686972","type":"journal-article","created":{"date-parts":[[2012,12,25]],"date-time":"2012-12-25T16:06:21Z","timestamp":1356451581000},"page":"1-9","source":"Crossref","is-referenced-by-count":15,"title":["Oxidative Stress Contributes to Endothelial Dysfunction in Mouse Models of Hereditary Hemorrhagic Telangiectasia"],"prefix":"10.1155","volume":"2012","author":[{"given":"Mirjana","family":"Jerkic","sequence":"first","affiliation":[{"name":"Molecular Structure and Function Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8"},{"name":"Heart and Stroke Richard Lewar Center of Excellence, University of Toronto, ON, Canada M5S 3E2"},{"name":"Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 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