Research Paper Volume 11, Issue 22 pp 10016—10030
Silencing of long non-coding RNA H19 downregulates CTCF to protect against atherosclerosis by upregulating PKD1 expression in ApoE knockout mice
- 1 Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang 550002, P. R. China
- 2 Department of Cardiology, The General Hospital of Ji’nan Military Region, Ji’nan 250031, P. R. China
- 3 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
received: March 20, 2019 ; accepted: October 21, 2019 ; published: November 22, 2019 ;https://doi.org/10.18632/aging.102388
How to Cite
Copyright © 2019 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.