PMID- 34307490 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210727 IS - 2297-055X (Print) IS - 2297-055X (Electronic) IS - 2297-055X (Linking) VI - 8 DP - 2021 TI - Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury. PG - 657544 LID - 10.3389/fcvm.2021.657544 [doi] LID - 657544 AB - Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury. Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis. Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H(2)O(2)-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H(2)O(2)-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H(2)O(2)-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis. Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H(2)O(2)-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways. CI - Copyright (c) 2021 Li, Liu, Sun, Wang, Zhu, Yang, Song, Wang, Wang, Zhao and Zhang. FAU - Li, Houwei AU - Li H AD - Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Liu, Xue AU - Liu X AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Sun, Na AU - Sun N AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Wang, Tianshuo AU - Wang T AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Zhu, Jia AU - Zhu J AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Yang, Shuang AU - Yang S AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Song, Xia AU - Song X AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Wang, Ruishuai AU - Wang R AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Wang, Xinhui AU - Wang X AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Zhao, Yixiu AU - Zhao Y AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. LA - eng PT - Journal Article DEP - 20210707 PL - Switzerland TA - Front Cardiovasc Med JT - Frontiers in cardiovascular medicine JID - 101653388 PMC - PMC8294331 OTO - NOTNLM OT - atherosclerosis OT - ceRNA OT - circRNA OT - microRNA OT - vascular endothelium COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/27 06:00 MHDA- 2021/07/27 06:01 PMCR- 2021/01/01 CRDT- 2021/07/26 06:39 PHST- 2021/01/23 00:00 [received] PHST- 2021/03/29 00:00 [accepted] PHST- 2021/07/26 06:39 [entrez] PHST- 2021/07/27 06:00 [pubmed] PHST- 2021/07/27 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcvm.2021.657544 [doi] PST - epublish SO - Front Cardiovasc Med. 2021 Jul 7;8:657544. doi: 10.3389/fcvm.2021.657544. eCollection 2021.