Cellular Physiology and Biochemistry (Nov 2018)

Notoginsenoside R1 Protects HUVEC Against Oxidized Low Density Lipoprotein (Ox-LDL)-Induced Atherogenic Response via Down-Regulating miR-132

  • Changgeng Fu,
  • Dexin Yin,
  • Haiying Nie,
  • Dajun Sun

DOI
https://doi.org/10.1159/000495677
Journal volume & issue
Vol. 51, no. 4
pp. 1739 – 1750

Abstract

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Background/Aims: Radix notoginseng is a well-known traditional Chinese herbal medicine, has extensively pharmacological activities in cardiovascular system. Notoginsenoside R1 (NGR1) is one main active ingredient of Radix notoginseng. The purpose of this study was to evaluate the functional effects of NGR1 on atherosclerosis (AS). Methods: Human umbilical vascular endothelial cells (HUVECs) were subjected to oxidized low density lipoprotein (ox-LDL), before which cells were preconditioned with NGR1. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were carried out to assess the impacts of ox-LDL and NGR1 on HUVECs. Besides, the expression of microRNA-132 (miR-132), and the regulatory role of miR-132 in Matrix Gla Protein (MGP) expression were measured by qRT-PCR and Western blot. Results: NGR1 pre-conditioning prevented ox-LDL-induced apoptosis, migration and overproduction of Monocyte Chemoattractant Protein 1 (MCP-1) and Intercellular Adhesion Molecule 1 (ICAM-1). miR-132 was up-regulated in response to ox-LDL while was down-regulated by NGR1 pre-conditioning. The protective actions of NGR1 in ox-LDL-treated HUVECs were enhanced by miR-132 inhibitor, while were attenuated by miR-132 mimic. Besides, the up-regulated miR-132 could further decrease the expression of MGP, which acted as an anti-migratory and anti-adhesive factor. Furthermore, ox-LDL-induced the activation of c-Jun N-terminal Kinase (JNK) and Nuclear Factor Kappa B (NF-κB) pathways were partially attenuated by NGR1, and were fully eliminated by NGR1 treatment together with MGP overexpression. Conclusion: NGR1 prevents ox-LDL-induced apoptosis, migration and adhesion-related molecule release in HUVECs possibly via down-regulating miR-132, and subsequent up-regulating MGP.

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