{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:56:08Z","timestamp":1783605368596,"version":"3.55.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Despite considerable research, the goal of finding nonsurgical remedies against thoracic aortic aneurysm and acute aortic dissection remains elusive. We sought to identify a novel aortic PK (protein kinase) that can be pharmacologically targeted to mitigate aneurysmal disease in a well-established mouse model of early-onset progressively severe Marfan syndrome (MFS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              Computational analyses of transcriptomic data derived from the ascending aorta of MFS mice predicted a probable association between thoracic aortic aneurysm and acute aortic dissection development and the multifunctional, stress-activated HIPK2 (homeodomain-interacting protein kinase 2). Consistent with this prediction,\n              <jats:italic>Hipk2<\/jats:italic>\n              gene inactivation significantly extended the survival of MFS mice by slowing aneurysm growth and delaying transmural rupture. HIPK2 also ranked among the top predicted PKs in computational analyses of DEGs (differentially expressed genes) in the dilated aorta of 3 MFS patients, which strengthened the clinical relevance of the experimental finding. Additional in silico analyses of the human and mouse data sets identified the TGF (transforming growth factor)-\u03b2\/Smad3 signaling pathway as a potential target of HIPK2 in the MFS aorta. Chronic treatment of MFS mice with an allosteric inhibitor of HIPK2-mediated stimulation of Smad3 signaling validated this prediction by mitigating thoracic aortic aneurysm and acute aortic dissection pathology and partially improving aortic material stiffness.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>HIPK2 is a previously unrecognized determinant of aneurysmal disease and an attractive new target for antithoracic aortic aneurysm and acute aortic dissection multidrug therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.121.316464","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T09:00:14Z","timestamp":1627549214000},"page":"2483-2493","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of HIPK2 Alleviates Thoracic Aortic Disease in Mice With Progressively Severe Marfan Syndrome"],"prefix":"10.1161","volume":"41","author":[{"given":"Cristina I.","family":"Caescu","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences, Institute for Systems Biomedicine (C.I.C., J.H., B.C., T.H., R.I., F.R.), Icahn School of Medicine at Mount Sinai, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Institute for Systems Biomedicine (C.I.C., J.H., B.C., T.H., R.I., F.R.), Icahn School of Medicine at Mount Sinai, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Crockett","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Institute for Systems Biomedicine (C.I.C., J.H., B.C., T.H., R.I., F.R.), Icahn School of Medicine at Mount Sinai, New 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J.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Borkar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of New York, Buffalo (R.B., J.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of New York, Buffalo (R.B., J.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Jondeau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et Pathologies Apparent\u00e9es, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France (P.A., G.J., C.B.)."},{"name":"LVTS, INSERM U1148, Universit\u00e9 de Paris, H\u00f4pital Bichat, France (P.A., G.J., 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