{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:48:46Z","timestamp":1792007326939,"version":"4.4.0"},"reference-count":68,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"856","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1531-456687919"],"award-info":[{"award-number":["SFB 1531-456687919"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["456687919"],"award-info":[{"award-number":["456687919"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>\n                    The neuropeptide neurotensin (NTS) is up-regulated in cardiac lymphatic endothelial cells (LECs) in response to ischemic or mechanical damage, but its role in cardiac remodeling is unknown. Here, we aimed to define the role of LEC-derived NTS in cardiac injury responses and to assess the therapeutic potential of targeting cardiac NTS signaling. In cultured murine and human cells, NTS reduced cardiomyocyte hypertrophy and fibroblast activation, and these effects were mediated by NTS receptor 2 (NTSR2)\u2013dependent guanosine 3\u2032,5\u2032-monophosphate (cGMP) production. Consistent with an antihypertrophic and antifibrotic role of NTS, mice with LEC-specific\n                    <jats:italic toggle=\"yes\">Nts<\/jats:italic>\n                    deletion exhibited aggravated hypertrophy and fibrosis after transverse aortic constriction (TAC) and myocardial infarction (MI). Similarly, cardiomyocyte-specific or activated fibroblast-specific inactivation of\n                    <jats:italic toggle=\"yes\">Ntsr2<\/jats:italic>\n                    led to enhanced cardiac remodeling after TAC. NTSR2 agonist NT150 reproduced the beneficial effects of NTS in cultured human and murine cells and ameliorated cardiac remodeling and dysfunction in both TAC and MI. Additionally, in freshly isolated cardiac tissues from patients with heart failure, NT150 induced cGMP production and suppressed prohypertrophic signaling. These findings identify NTS as an endogenous inhibitor of adverse cardiac remodeling and suggest NTSR2 agonism as a therapeutic strategy in heart failure.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aea9877","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:59:10Z","timestamp":1782928750000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Neurotensin receptor 2 agonism attenuates adverse cardiac remodeling in preclinical models"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7951-4598","authenticated-orcid":true,"given":"Niharika","family":"Shiva","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, 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Institute, Goethe University, Frankfurt am Main, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kubin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Kerckhoff, Bad Nauheim and Medical Clinic I, Justus-Liebig-University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Shimari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-4549","authenticated-orcid":true,"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiangang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1709-1477","authenticated-orcid":true,"given":"Pieterjan","family":"Dierickx","sequence":"additional","affiliation":[{"name":"Circadian Regulation of Cardiometabolism Lab, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Frankfurt am Main, Germany."},{"name":"Cardiopulmonary Institute, Goethe University, Frankfurt am Main, 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