Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats

Background: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in hear...

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Main Authors: Ying Liu, Ying Dong, Zhaojie Dong, Jiawei Song, Zhenzhou Zhang, Lirong Liang, Xiaoyan Liu, Lanlan Sun, Xueting Li, Miwen Zhang, Yihang Chen, Ran Miao, Jiuchang Zhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2021.814402/full
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author Ying Liu
Ying Liu
Ying Liu
Ying Dong
Ying Dong
Zhaojie Dong
Zhaojie Dong
Jiawei Song
Jiawei Song
Jiawei Song
Zhenzhou Zhang
Zhenzhou Zhang
Lirong Liang
Lirong Liang
Xiaoyan Liu
Xiaoyan Liu
Lanlan Sun
Xueting Li
Xueting Li
Miwen Zhang
Miwen Zhang
Yihang Chen
Yihang Chen
Ran Miao
Ran Miao
Jiuchang Zhong
Jiuchang Zhong
Jiuchang Zhong
author_facet Ying Liu
Ying Liu
Ying Liu
Ying Dong
Ying Dong
Zhaojie Dong
Zhaojie Dong
Jiawei Song
Jiawei Song
Jiawei Song
Zhenzhou Zhang
Zhenzhou Zhang
Lirong Liang
Lirong Liang
Xiaoyan Liu
Xiaoyan Liu
Lanlan Sun
Xueting Li
Xueting Li
Miwen Zhang
Miwen Zhang
Yihang Chen
Yihang Chen
Ran Miao
Ran Miao
Jiuchang Zhong
Jiuchang Zhong
Jiuchang Zhong
author_sort Ying Liu
collection DOAJ
description Background: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in heart and vasculature, thereby regulating their target gene and protein expression, via competitive endogenous RNA (ceRNA) mechanism. However, the exact roles and underlying mechanisms of circRNAs in hypertension and related cardiovascular diseases remain largely unknown.Methods and Results: High-throughput RNA sequencing (RNA-seq) was used to analyze the differentially expressed (DE) circRNAs in aortic vascular tissues of spontaneously hypertensive rats (SHR). Compared with the Wistar-Kyoto (WKY) rats, there were marked increases in the levels of systolic blood pressure, diastolic blood pressure and mean blood pressure in SHR under awake conditions via the tail-cuff methodology. Totally, compared with WKY rats, 485 DE circRNAs were found in aortic vascular tissues of SHR with 279 up-regulated circRNAs and 206 down-regulated circRNAs. Furthermore, circRNA-target microRNAs (miRNAs) and the target messenger RNAs (mRNAs) of miRNAs were predicted by the miRanda and Targetscan softwares, respectively. Additionally, real-time RT-PCR analysis verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005818, rno_circRNA_0005304, rno_circRNA_0005506, and rno_circRNA_0009301 were observed in aorta of SHR when compared with that of WKY rats. Then, the potential ceRNA regulatory mechanism was constructed via integrating 5 validated circRNAs, 31 predicted miRNAs, and 266 target mRNAs. More importantly, three hub genes (NOTCH1, FOXO3, and STAT3) were recognized according to PPI network and three promising circRNA-miRNA-mRNA regulatory axes were found in hypertensive rat aorta, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0009197/ miR-509-5p/FOXO3, and rno_circRNA_0005818/miR-10b-5p/STAT3, respectively.Conclusions: Our results demonstrated for the first time that circRNAs are expressed aberrantly in aortic vascular tissues of hypertensive rats and may serve as a sponge linking with relevant miRNAs participating in pathogenesis of hypertension and related ischemic heart diseases via the circRNA-miRNA-mRNA ceRNAnetwork mechanism.
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spelling doaj.art-1496441eb0804aeb88c7ea5a99782f922022-12-21T18:45:37ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-12-01810.3389/fcvm.2021.814402814402Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive RatsYing Liu0Ying Liu1Ying Liu2Ying Dong3Ying Dong4Zhaojie Dong5Zhaojie Dong6Jiawei Song7Jiawei Song8Jiawei Song9Zhenzhou Zhang10Zhenzhou Zhang11Lirong Liang12Lirong Liang13Xiaoyan Liu14Xiaoyan Liu15Lanlan Sun16Xueting Li17Xueting Li18Miwen Zhang19Miwen Zhang20Yihang Chen21Yihang Chen22Ran Miao23Ran Miao24Jiuchang Zhong25Jiuchang Zhong26Jiuchang Zhong27Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Echocardiography, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaHeart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaBackground: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in heart and vasculature, thereby regulating their target gene and protein expression, via competitive endogenous RNA (ceRNA) mechanism. However, the exact roles and underlying mechanisms of circRNAs in hypertension and related cardiovascular diseases remain largely unknown.Methods and Results: High-throughput RNA sequencing (RNA-seq) was used to analyze the differentially expressed (DE) circRNAs in aortic vascular tissues of spontaneously hypertensive rats (SHR). Compared with the Wistar-Kyoto (WKY) rats, there were marked increases in the levels of systolic blood pressure, diastolic blood pressure and mean blood pressure in SHR under awake conditions via the tail-cuff methodology. Totally, compared with WKY rats, 485 DE circRNAs were found in aortic vascular tissues of SHR with 279 up-regulated circRNAs and 206 down-regulated circRNAs. Furthermore, circRNA-target microRNAs (miRNAs) and the target messenger RNAs (mRNAs) of miRNAs were predicted by the miRanda and Targetscan softwares, respectively. Additionally, real-time RT-PCR analysis verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005818, rno_circRNA_0005304, rno_circRNA_0005506, and rno_circRNA_0009301 were observed in aorta of SHR when compared with that of WKY rats. Then, the potential ceRNA regulatory mechanism was constructed via integrating 5 validated circRNAs, 31 predicted miRNAs, and 266 target mRNAs. More importantly, three hub genes (NOTCH1, FOXO3, and STAT3) were recognized according to PPI network and three promising circRNA-miRNA-mRNA regulatory axes were found in hypertensive rat aorta, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0009197/ miR-509-5p/FOXO3, and rno_circRNA_0005818/miR-10b-5p/STAT3, respectively.Conclusions: Our results demonstrated for the first time that circRNAs are expressed aberrantly in aortic vascular tissues of hypertensive rats and may serve as a sponge linking with relevant miRNAs participating in pathogenesis of hypertension and related ischemic heart diseases via the circRNA-miRNA-mRNA ceRNAnetwork mechanism.https://www.frontiersin.org/articles/10.3389/fcvm.2021.814402/fullcompeting endogenous RNAs networkmicroRNAcircular RNAhypertensive vascular injuryischemia heart disease
spellingShingle Ying Liu
Ying Liu
Ying Liu
Ying Dong
Ying Dong
Zhaojie Dong
Zhaojie Dong
Jiawei Song
Jiawei Song
Jiawei Song
Zhenzhou Zhang
Zhenzhou Zhang
Lirong Liang
Lirong Liang
Xiaoyan Liu
Xiaoyan Liu
Lanlan Sun
Xueting Li
Xueting Li
Miwen Zhang
Miwen Zhang
Yihang Chen
Yihang Chen
Ran Miao
Ran Miao
Jiuchang Zhong
Jiuchang Zhong
Jiuchang Zhong
Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
Frontiers in Cardiovascular Medicine
competing endogenous RNAs network
microRNA
circular RNA
hypertensive vascular injury
ischemia heart disease
title Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
title_full Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
title_fullStr Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
title_full_unstemmed Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
title_short Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats
title_sort expression profiles of circular rna in aortic vascular tissues of spontaneously hypertensive rats
topic competing endogenous RNAs network
microRNA
circular RNA
hypertensive vascular injury
ischemia heart disease
url https://www.frontiersin.org/articles/10.3389/fcvm.2021.814402/full
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