open access

Vol 59, No 2 (2021)
Original paper
Submitted: 2021-05-14
Accepted: 2021-06-11
Published online: 2021-06-21
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Golgi a-mannosidase II mediates the formation of vascular smooth muscle foam cells under inflammatory stress

Kelan Zha1, Qiang Ye1
DOI: 10.5603/FHC.a2021.0015
·
Pubmed: 34151999
·
Folia Histochem Cytobiol 2021;59(2):134-143.
Affiliations
  1. Department of Cardiology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping street, Jiangyang District, 646000 Luzhou, China

open access

Vol 59, No 2 (2021)
ORIGINAL PAPERS
Submitted: 2021-05-14
Accepted: 2021-06-11
Published online: 2021-06-21

Abstract

Introduction. Vascular smooth muscle cells (VSMCs)-based foam cell formation is a crucial factor in the atherosclerosis process. We aimed to explore the mechanism of Golgi a-mannosidase II (GMII) effects on the VSMCs-based foam cell formation.

Material and methods. VSMCs were exposed to different concentrations of low-density lipoproteins (LDLs), lipopolysaccharide (LPS), and/or GMII inhibitor (swainsonine). The qRT-PCR and western blot were used for expression analysis. Oil Red O staining was used to verify changes of lipid droplets in VSMCs. The translocation of the SCAP from the endoplasmic reticulum (ER) to Golgi was detected by immunofluorescence (IF).

Results. LPS disrupted the LDLs-mediated regulation of LDL receptor (LDLr) and increased intracellular cholesterol ester, which was inversely inhibited by swainsonine. The activity of a-mannosidase II and GMII expression were decreased by LDLs but increased by the addition of LPS. Conversely, LPS-induced enhancement was reversed by swainsonine. Additionally, swainsonine reversed the LPS-induced increase of intracellular lipid droplets in the presence of LDLs. Expression analysis demonstrated that LDLr, SCAP, and SREBP2 were up-regulated by LPS, but reversed by swainsonine in LDLs-treated cells. IF staining revealed that swainsonine inhibited the translocation of SCAP to Golgi under inflammatory stress.

Conclusions. Collectively, swainsonine restrained LDLr expression to suppress the formation of VSMCs-based foam cells by reducing SREBP2 and SCAP under inflammatory stress conditions, suggesting that GMII contributes to the formation of VSMCs-based foam cells under inflammatory stress.

Abstract

Introduction. Vascular smooth muscle cells (VSMCs)-based foam cell formation is a crucial factor in the atherosclerosis process. We aimed to explore the mechanism of Golgi a-mannosidase II (GMII) effects on the VSMCs-based foam cell formation.

Material and methods. VSMCs were exposed to different concentrations of low-density lipoproteins (LDLs), lipopolysaccharide (LPS), and/or GMII inhibitor (swainsonine). The qRT-PCR and western blot were used for expression analysis. Oil Red O staining was used to verify changes of lipid droplets in VSMCs. The translocation of the SCAP from the endoplasmic reticulum (ER) to Golgi was detected by immunofluorescence (IF).

Results. LPS disrupted the LDLs-mediated regulation of LDL receptor (LDLr) and increased intracellular cholesterol ester, which was inversely inhibited by swainsonine. The activity of a-mannosidase II and GMII expression were decreased by LDLs but increased by the addition of LPS. Conversely, LPS-induced enhancement was reversed by swainsonine. Additionally, swainsonine reversed the LPS-induced increase of intracellular lipid droplets in the presence of LDLs. Expression analysis demonstrated that LDLr, SCAP, and SREBP2 were up-regulated by LPS, but reversed by swainsonine in LDLs-treated cells. IF staining revealed that swainsonine inhibited the translocation of SCAP to Golgi under inflammatory stress.

Conclusions. Collectively, swainsonine restrained LDLr expression to suppress the formation of VSMCs-based foam cells by reducing SREBP2 and SCAP under inflammatory stress conditions, suggesting that GMII contributes to the formation of VSMCs-based foam cells under inflammatory stress.

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Keywords

vascular smooth muscle cells; foam cells; LDLr; Golgi a-mannosidase

About this article
Title

Golgi a-mannosidase II mediates the formation of vascular smooth muscle foam cells under inflammatory stress

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 59, No 2 (2021)

Article type

Original paper

Pages

134-143

Published online

2021-06-21

DOI

10.5603/FHC.a2021.0015

Pubmed

34151999

Bibliographic record

Folia Histochem Cytobiol 2021;59(2):134-143.

Keywords

vascular smooth muscle cells
foam cells
LDLr
Golgi a-mannosidase

Authors

Kelan Zha
Qiang Ye

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