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

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

doi:10.3389/fcvm.2021.814402

Frontiers in Cardiovascular Medicine (Dec 2021)

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

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

Affiliations

Ying Liu: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ying Liu: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ying Liu: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ying Dong: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ying Dong: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Zhaojie Dong: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Zhaojie Dong: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiawei Song: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiawei Song: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiawei Song: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Zhenzhou Zhang: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Zhenzhou Zhang: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Lirong Liang: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Lirong Liang: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Xiaoyan Liu: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Xiaoyan Liu: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Lanlan Sun: Department of Echocardiography, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Xueting Li: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Xueting Li: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Miwen Zhang: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Miwen Zhang: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Yihang Chen: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Yihang Chen: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ran Miao: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Ran Miao: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiuchang Zhong: Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiuchang Zhong: Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
Jiuchang Zhong: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

DOI: https://doi.org/10.3389/fcvm.2021.814402
Journal volume & issue: Vol. 8

Abstract

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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.

Published in Frontiers in Cardiovascular Medicine

ISSN: 2297-055X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.frontiersin.org/journals/cardiovascular-medicine

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