Regulation of circadian rhythms by NEAT1 mediated TMAO-induced endothelial proliferation: A protective role of asparagus extract.

Abstract

Trimethylamine N-oxide (TMAO) promotes atherosclerosis in association with the functions of endothelial cells. Clock and Bmal1, as two main components of molecular circadian clock, play important regulatory roles during progression of atherogenesis. However, whether Clock and Bmal1 are involved in the regulation of endothelial proliferation disturbed by TMAO are unclear. We observed that cell proliferation of human umbilical vein endothelial cells (HUVECs) was inhibited after exposed to TMAO for 24 h. Besides, TMAO caused increased expression of lncRNA-NEAT1, Clock and Bmal1, and inhibited MAPK pathways. While MAPK pathways were blocked, the expression of Clock and Bmal1 was elevated. NEAT1 showed a circadian rhythmic expression in HUVECs, and its overexpression reduced cell proliferation. Knockdown or overexpression of NEAT1 might decrease or increase the expression of Clock and Bmal1 respectively, while raised or suppressed the expression of MAPK pathways correspondingly. Asparagus extract (AE) was found to improve the TMAO-reduced HUVECs proliferation. Moreover, it ameliorated the disorders of NEAT1, Clock, Bmal1, and MAPK signaling pathways induced by TMAO. Therefore, our findings indicated that NEAT1 regulating Clock-Bmal1 via MAPK pathways was involved in TMAO-repressed HUVECs proliferation, and AE improved endothelial proliferation by TMAO, proposing a novel mechanism for cardiovascular disease prevention.

• Authors: Xiaoyue Wu, Lijun Chen, Falak Zeb, Yunxiang Huang, Jing An, Jianglei Ren, Feng Yang, Qing Feng
• Journal: Experimental cell research (Exp Cell Res) Vol. 382 Issue 1 Pg. 111451 (09 01 2019) ISSN: 1090-2422 [Electronic] United States
• PMID: 31173767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• ARNTL Transcription Factors
• ARNTL protein, human
• Methylamines
• NEAT1 long non-coding RNA, human
• Plant Extracts
• RNA, Long Noncoding
• RNA, Small Interfering
• CLOCK Proteins
• CLOCK protein, human
• trimethyloxamine

Topics

• ARNTL Transcription Factors (antagonists & inhibitors, biosynthesis, genetics)
• Asparagaceae (chemistry)
• Atherosclerosis (genetics, physiopathology)
• CLOCK Proteins (biosynthesis, genetics)
• Cell Division (drug effects)
• Circadian Rhythm (drug effects, physiology)
• Gene Expression Regulation (drug effects, genetics, physiology)
• Humans
• MAP Kinase Signaling System (drug effects, physiology)
• Methylamines (pharmacology, toxicity)
• Plant Extracts (pharmacology)
• Plant Stems (chemistry)
• RNA Interference
• RNA, Long Noncoding (antagonists & inhibitors, genetics, physiology)
• RNA, Small Interfering (genetics, pharmacology)