دورية أكاديمية
أعرض في EDS

Macrophage-mediated downregulation of lncRNA Carmn in mouse abdominal aortic aneurysm.

التفاصيل البيبلوغرافية
العنوان: Macrophage-mediated downregulation of lncRNA Carmn in mouse abdominal aortic aneurysm.
المؤلفون: Yang H; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States., Zhou T; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States., Liu B; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States. Electronic address: bliu24@wisc.edu.
المصدر: Vascular pharmacology [Vascul Pharmacol] 2024 Mar; Vol. 154, pp. 107264. Date of Electronic Publication: 2023 Dec 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3649 (Electronic) Linking ISSN: 15371891 NLM ISO Abbreviation: Vascul Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier Science, c2002-
مواضيع طبية MeSH: RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Aortic Aneurysm, Abdominal*/metabolism, Mice ; Animals ; Down-Regulation ; Muscle, Smooth, Vascular/metabolism ; Macrophages/metabolism ; Contractile Proteins/genetics ; Contractile Proteins/metabolism ; Myocytes, Smooth Muscle/metabolism ; Aorta, Abdominal/metabolism
مستخلص: The long noncoding RNA (lncRNA) CARMN (cardiac mesoderm enhancer associated noncoding RNA) is a highly conserved lncRNA that expresses primarily by smooth muscle cells (SMCs). Recent literature demonstrates that CARMN plays a critical role in the differentiation and maintaining of the contractile state of vascular SMCs. Because aortic SMCs show diminished contractile proteins in abdominal aortic aneurysms (AAAs), we hypothesize that the expression of CARMN is downregulated in the aortic wall affected by aneurysm. In this study, we analyzed publicly available single-cell or bulk RNA sequencing data comparing healthy and aneurysmal mouse aortic tissues. In both healthy and diseased aortas, Carmn expression was enriched in SMCs characterized by the high expression of SMC-specific contractile proteins including Myh11 and Acta2. Carmn expression levels varied among the sub-clusters of SMCs and consequently along the aortic tree. Comparing to the corresponding sham aorta, aortas from 3 distinct AAA models contained less Carmn. To validate the Carmn downregulation, we induced AAA using the Angiotensin II and CaCl 2 models. In situ hybridization showed that Carmn mRNA located in the nuclei of SMCs and became downregulated within a few days following the aneurysm induction. Mechanistically, we tested whether Carmn expression is regulated by infiltrating macrophages --- the predominant inflammatory cells found in aneurysmal tissues --- by treating healthy mouse aortic SMCs with media conditioned by macrophages primed with pro-inflammatory or anti-inflammatory cytokines. PCR analysis showed that inflammatory macrophages reduced the expression of Carmn and contractile genes including Myh11 and Acta2. Taken together, our results from bioinformatic and experimental analyses demonstrate that Carmn is downregulated in different AAA models, likely by inflammatory macrophages. The negative regulation of Carmn in AAA tissues may explain at least in part the loss of SMC contractile state during the pathogenesis of this progressive degenerative disease.
Competing Interests: Declaration of Competing Interest The authors state that the research was carried out without any commercial or financial affiliations that could be perceived as a potential conflict of interest.
(Copyright © 2023. Published by Elsevier Inc.)
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معلومات مُعتمدة: R01 HL149404 United States HL NHLBI NIH HHS; R01 HL158073 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Abdominal aortic aneurysm; Long noncoding RNA; Vascular diseases
المشرفين على المادة: 0 (RNA, Long Noncoding)
0 (Contractile Proteins)
تواريخ الأحداث: Date Created: 20231214 Date Completed: 20240311 Latest Revision: 20240430
رمز التحديث: 20240501
مُعرف محوري في PubMed: PMC10939852
DOI: 10.1016/j.vph.2023.107264
PMID: 38097098
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3649
DOI:10.1016/j.vph.2023.107264