Down-regulation of lncRNA MALAT1 alleviates vascular lesion and vascular remodeling of rats with hypertension

Aging (Albany NY). 2019 Jul 25;11(14):5192-5205. doi: 10.18632/aging.102113.

Abstract

Objective: Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats.

Results: LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats.

Methods: LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays.

Conclusion: This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.

Keywords: Notch-1; hypertension; lncRNA MALAT1; vascular lesion; vascular remodeling.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis
  • Down-Regulation
  • Endothelial Cells / cytology*
  • Female
  • Humans
  • Hypertension / chemically induced
  • Hypertension / genetics*
  • Male
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering
  • Rats
  • Receptor, Notch1 / metabolism
  • Signal Transduction
  • Vascular Remodeling*

Substances

  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Receptor, Notch1