{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:12:18Z","timestamp":1779196338946,"version":"3.51.4"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"20","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08"],"award-info":[{"award-number":["K08"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DP2"],"award-info":[{"award-number":["DP2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,18]]},"abstract":"<jats:p>\n                    Aortic dissection (AD) is a life-threatening vascular disease with limited treatment strategies. Here, we show that loss of the GWAS-identified\n                    <jats:italic>SH2B3<\/jats:italic>\n                    gene, encoding lymphocyte adaptor protein LNK, markedly increases susceptibility to acute AD and rupture in response to angiotensin (Ang) II infusion. As early as day 3 following Ang II infusion, prior to the development of AD,\n                    <jats:italic>\n                      Lnk\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    aortas display altered mechanical properties, increased elastin breaks, collagen thinning, enhanced neutrophil accumulation, and increased MMP-9 activity compared with WT mice. Adoptive transfer of\n                    <jats:italic>\n                      Lnk\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    leukocytes into\n                    <jats:italic>\n                      Rag1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice induces AD and rupture in response to Ang II, demonstrating that LNK deficiency in hematopoietic cells plays a key role in this disease. Interestingly, treatment with doxycycline prevents the early accumulation of aortic neutrophils and significantly reduces the incidence of AD and rupture. PrediXcan analysis in a biobank of more than 23,000 individuals reveals that decreased expression of\n                    <jats:italic>SH2B3<\/jats:italic>\n                    is significantly associated with increased frequency of AD-related phenotypes (odds ratio 0.81). Thus, we identified a role for LNK in the pathology of AD in experimental animals and humans and describe a new model that can be used to inform both inherited and acquired forms of this disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.122558","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T11:01:49Z","timestamp":1539774109000},"source":"Crossref","is-referenced-by-count":20,"title":["LNK deficiency promotes acute aortic dissection and rupture"],"prefix":"10.1172","volume":"3","author":[{"given":"Fanny","family":"Laroumanie","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arina","family":"Korneva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale University, New Haven, Connecticut, 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