Dataset Information

The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis.

ABSTRACT: Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow (p < 0.01 each). The HS expression was higher under laminar flow after a 1 day (p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down (p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders (p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis.

SUBMITTER: Urschel K

PROVIDER: S-EPMC10380765 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis.

Urschel Katharina K Hug Karsten P KP Zuo Hanxiao H Büttner Michael M Furtmair Roman R Kuehn Constanze C Stumpfe Florian M FM Botos Balaz B Achenbach Stephan S Yuan Yan Y Dietel Barbara B Tauchi Miyuki M

International journal of molecular sciences 20230718 14

Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesi ...[more]

PMID: 37511353

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Project description:BackgroundAbnormal endothelial shear stress (ESS) is a significant risk factor for atherosclerosis (AS); however, the genes and pathways between ESS and AS are poorly understood. Here, we screened hub genes and potential regulatory targets linked to the progression of AS induced by abnormal ESS.MethodsThe microarray data of ESS and AS were downloaded from the Gene Expression Omnibus (GEO) database. The coexpression modules related to shear stress and AS were identified with weighted gene coexpression network analysis (WGCNA). Coexpression genes in modules obtained from GSE28829 and GSE160611 were considered as SET1. The results were validated in validation set by differential gene analysis. The limma package in R was used to identify differentially expressed genes (DEGs). The common DEGs of GSE100927 and GSE103672 were regarded as SET2. Next, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted. Protein-protein interaction (PPI) enrichment analysis was assembled, and hub genes were identified using MCODE and ClueGO in Cytoscape. ROC curve analyses were conducted to assess the ability of common hub genes to distinguish samples of atherosclerotic plaque from normal arterial. The expression of common hub gene was verified in ox-LDL-induced foam cells and GSE41571.ResultsWe identified three gene modules (the blue, tan, and cyan modules) related to AS and three shear stress-related modules (the brown, red, and pink modules). A total of 129 genes in SET1 and 476 genes in SET2 were identified. CCRL2, LGALS9, and PLCB2 were identified as common hub genes and validated in the GSE100927, GSE28829, and GSE41571. ROC analysis indicates the expression of CCRL2, LGALS9, and PLCB2 could effectively distinguish the atherosclerotic plaque and normal arterial. The expression level of CCRL2, LGALS9, and PLCB2 increases with the accumulation of lipid increased.ConclusionWe identified CCRL2, LGALS9, and PLCB2 as key genes associated with abnormal ESS and AS and may provide potential prevention and treatment target of AS induced by abnormal ESS.

Dataset Information

The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis.

Publications

The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis.

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