2026-07-01 マックス・プランク研究所
＜関連情報＞
- https://www.mpg.de/26857285/neurotensin-prevents-harmful-cardiac-remodelling
- https://www.science.org/doi/10.1126/scitranslmed.aea9877
ニューロテンシン受容体2の作動薬は、前臨床モデルにおいて有害な心臓リモデリングを軽減する Neurotensin receptor 2 agonism attenuates adverse cardiac remodeling in preclinical models
Niharika Shiva, Haruya Kawase, Jürgen Einsiedel, Jeonghyeon Kwon, […] , and Nina Wettschureck
Science Translational Medicine Published:1 Jul 2026
DOI:https://doi.org/10.1126/scitranslmed.aea9877
Abstract
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)–dependent guanosine 3′,5′-monophosphate (cGMP) production. Consistent with an antihypertrophic and antifibrotic role of NTS, mice with LEC-specific Nts deletion exhibited aggravated hypertrophy and fibrosis after transverse aortic constriction (TAC) and myocardial infarction (MI). Similarly, cardiomyocyte-specific or activated fibroblast-specific inactivation of Ntsr2 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.
