مورد إلكتروني
Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPAR gamma signature
| العنوان: | Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPAR gamma signature |
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| بيانات النشر: | Linköpings universitet, Avdelningen för barns och kvinnors hälsa Linköpings universitet, Medicinska fakulteten Linköpings universitet, Avdelningen för prevention, rehabilitering och nära vård Linköpings universitet, Medicinska fakulteten Arbets- och miljömedicin Univ Zurich, Switzerland Univ Zurich, Switzerland Univ Hosp Zurich, Switzerland; Jagiellonian Univ, Poland Shanghai Jiao Tong Univ, Peoples R China Swiss Fed Inst Technol, Switzerland; Univ Hosp Zurich, Switzerland Univ Zurich, Switzerland; IRCCS San Raffaele Pisana, Italy Univ Zurich, Switzerland Univ Zurich, Switzerland Univ Estadual Campinas, Brazil Univ Estadual Campinas, Brazil Univ Hosp Zurich, Switzerland Univ Hosp Zurich, Switzerland Univ Hosp Zurich, Switzerland Sungkyunkwan Univ, South Korea Univ Groningen, Netherlands Univ Zurich, Switzerland; Swiss Fed Inst Technol, Switzerland; Univ Hosp Zurich, Switzerland Univ Zurich, Switzerland; Royal Brompton and Harefield Hosp Trust, England; Imperial Coll London, England Univ Zurich, Switzerland OXFORD UNIV PRESS 2020 |
| تفاصيل مُضافة: | Oppi, Sara Nusser-Stein, Stefanie Blyszczuk, Przemyslaw Wang, Xu Jomard, Anne Marzolla, Vincenzo Yang, Kangmin Velagapudi, Srividya Ward, Liam Yuan, Ximing Geiger, Martin A. Guillaumon, Ana T. Othman, Alaa Hornemann, Thorsten Rancic, Zoran Ryu, Dongryeol Oosterveer, Maaike H. Osto, Elena Luscher, Thomas F. Stein, Sokrates |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Aims Nuclear receptors and their cofactors regulate key pathophysiological processes in atherosclerosis development. The transcriptional activity of these nuclear receptors is controlled by the nuclear receptor corepressors (NCOR), scaffolding proteins that form the basis of large corepressor complexes. Studies with primary macrophages demonstrated that the deletion of Ncor1 increases the expression of atherosclerotic molecules. However, the role of nuclear receptor corepressors in atherogenesis is unknown. Methods and results We generated myeloid cell-specific Ncor1 knockout mice and crossbred them with low-density lipoprotein receptor and results (Ldlr) knockouts to study the role of macrophage NCOR1 in atherosclerosis. We demonstrate that myeloid cellspecific deletion of nuclear receptor corepressor 1 (NCOR1) aggravates atherosclerosis development in mice. Macrophage Ncorl-deficiency leads to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 are mediated via suppression of peroxisome proliferator-activated receptor gamma (PPAR gamma) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized low-density lipoprotein uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 is reduced whereas the PPAR gamma signature is increased, and this signature is more pronounced in ruptured compared with non-ruptured carotid plaques. Conclusions Our findings show that macrophage NCOR1 blocks the pro-atherogenic functions of PPAR gamma in atherosclerosis and suggest that stabilizing the NCOR1-PPAR gamma binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients. Funding Agencies|Swiss National Science FoundationSwiss National Science Foundation (SNSF) [PZOOP3_161521, PZOOP3_161506, PR00P3_179861/1]; Novartis Foundation for medical-biological Research [16B103]; Swiss Life Foundation; Olga-Mayenfisch Foundation; OPO foundation [2018-0054]; Swiss Heart Foundation; Zurich Heart House-Foundation for Cardiovascular Research, Zurich; Rosalind Franklin Fellowship from the University of Groningen |
| مصطلحات الفهرس: | Atherosclerosis; Immunometabolic disease; Mechanism of disease; Nuclear receptor corepressor; Ncor1, Medical Bioscience, Medicinsk biovetenskap, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.1093.eurheartj.ehz667 |
| URL: | European Heart Journal, 0195-668X, 2020, 41:9, s. 995-1005 |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | English |
| أرقام أخرى: | UPE oai:DiVA.org:liu-165186 doi:10.1093/eurheartj/ehz667 PMID 31529020 ISI:000522644600008 1234729252 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1234729252 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1093.eurheartj.ehz667 |
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