Silencing of long non-coding RNA H19 downregulates CTCF to protect against atherosclerosis by upregulating PKD1 expression in ApoE knockout mice

• Type of Material: Article
• Authors: Yongyao Yang, Guizhou Provincial People's Hospital; Feng Tang, Guizhou Provincial People's Hospital; Fang Wei, Guizhou Provincial People's Hospital; Long Yang, Guizhou Provincial People's Hospital; Chunyan Kuang, Guizhou Provincial People's Hospital; Hongming Zhang, The General Hospital of Ji’nan Military Region; Jiusheng Deng, Emory University; Qiang Wu, Guizhou Provincial People's Hospital
• Language: English
• Date: 2019-11-30
• Publisher: Impact Journals LLC
• Publication Version: Final Published Version
• Copyright Statement: © Yang et al.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/aging.102388
• Title of Journal or Parent Work: Aging US
• Volume: 11
• Issue: 22
• Start Page: 10016
• End Page: 10030
• Grant/Funding Information: This study was supported by the National Natural Science Foundation of China [NO. 81660080], the National Key-Specialty Construction Project of China [NO. (2013)544] and the Clinical Research Center Project of the Department of Science and Technology of Guizhou Province [NO. (2017)5405].
• Keywords: ENDOTHELIAL-CELLS; CCCTC-binding factor; Geriatrics & Gerontology; long non-coding RNA H19; CCCTC-BINDING FACTOR; ANGIOGENESIS; atherosclerosis; Life Sciences & Biomedicine; APOPTOSIS; Science & Technology; Cell Biology; GENE; VULNERABLE PLAQUE-FORMATION; LNCRNA H19; MARKER; atherosclerotic vulnerable plaque formation; polycystic kidney disease 1; REGION; ASSOCIATION
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

This study aimed to explore the interactions among long non-coding RNA H19, transcriptional factor CCCTC-binding factor (CTCF) and polycystic kidney disease 1 (PKD1), and to investigate its potentially regulatory effect on vulnerable plaque formation and angiogenesis of atherosclerosis. We established an atherosclerosis mouse model in ApoE knockout mice, followed by gain-and loss-of-function approaches. H19 was upregulated in aortic tissues of atherosclerosis mice, but silencing of H19 significantly inhibited atherosclerotic vulnerable plaque formation and intraplaque angiogenesis, accompanied by a downregulated expression of MMP-2, VEGF, and p53 and an upregulated expression of TIMP-1. Moreover, opposite results were found in the aortic tissues of atherosclerosis mice treated with H19 or CTCF overexpression. H19 was capable of recruiting CTCF to suppress PKD1, thus promoting atherosclerotic vulnerable plaque formation and intraplaque angiogenesis in atherosclerosis mice. The present study provides evidence that H19 recruits CTCF to downregulate the expression of PKD1, thereby promoting vulnerable plaque formation and intraplaque angiogenesis in mice with atherosclerosis.