Prediction of Mechanosensitive Genes in Vascular Endothelial Cells Under High Wall Shear Stress.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35087573", "kind": "science-record", "revision": 6, "content_hash": "sha256:dc61245ef41e26f0dfc702430d634009d5d92fe2b378de3a1e9862a327b08c80", "created_at": "2026-11-01T17:36:48Z", "updated_at": "2026-11-01T22:48:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prediction of Mechanosensitive Genes in Vascular Endothelial Cells Under High Wall Shear Stress.", "doi": "10.3389/fgene.2021.796812", "pmid": "35087573", "authors": ["Lei Shen", "Kaige Zhou", "Hong Liu", "Jie Yang", "Shuqi Huang", "Fei Yu", "Dongya Huang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Objective: The vulnerability of atherosclerotic plaques is among the leading cause of ischemic stroke. High wall shear stress (WSS) promotes the instability of atherosclerotic plaques by directly imparting mechanical stimuli, but the specific mechanisms remain unclear. We speculate that modulation of mechanosensitive genes may play a vital role in accelerating the development of plaques. The purpose of this study was to find mechanosensitive genes in vascular endothelial cells (ECs) through combining microarray data with bioinformatics technology and further explore the underlying dynamics-related mechanisms that cause the progression and destabilization of atherosclerotic plaques. Methods: Microarray data sets for human vascular ECs under high and normal WSS were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified through the R language. The performance of enrichment analysis and protein-protein interaction (PPI) network presented the biological function and signaling pathways of the DEGs. Hub genes were identified based on the PPI network and validated by GEO data sets. Predicted transcription factor (TF) genes and miRNAs interaction with potential mechanosensitive genes were identified by NetworkAnalyst. Results: A total of 260 DEGs, 121 upregulated and 139 downregulated genes, were screened between high and normal WSS from GSE23289. A total of 10 hub genes and four cluster modules were filtered out based on the PPI network. The enrichment analysis showed that the biological functions of the hub genes were mainly involved in responses to unfolded protein and topologically incorrect protein, and t to endoplasmic reticulum stress. The significant pathways associated with the hub genes were those of protein processing in the endoplasmic reticulum, antigen processing, and presentation. Three out of the 10 hub genes, namely, activated transcription factor 3 (ATF3), heat shock protein family A (Hsp70) member 6 (HSPA6), and dual specificity phosphatase 1 (DUSP1, also known as CL100, HVH1, MKP-1, PTPN10), were verified in GSE13712. The expression of DUSP1 was higher in the senescent cell under high WSS than that of the young cell. The TF-miRNA-mechanosensitive gene coregulatory network was constructed. Conclusion: In this work, we identified three hub genes, ATF3, HSPA6, and DUSP1, as the potential mechanosensitive genes in the human blood vessels. DUSP1 was confirmed to be associated with the senescence of vascular ECs. Therefore, these three mechanosensitive genes may have emerged as potential novel targets for the prediction and prevention of ischemic stroke. Furthermore, the TF-miRNA-mechanosensitive genes coregulatory network reveals an underlying regulatory mechanism and the pathways to control disease progression.", "claims": [{"id": "claim-method", "statement": "The R package “limma” (bioconductor) was performed to analyze the differentially expressed genes (DEGs) between the normal and high WSS groups (Smyth et al., 2005). The DEGs were screening out according to the following two cutoff criteria: adjusted p-value <0.05 and absolute log2 [fold change (FC)] >1 (Rougeot et al., 2019; Gao et al., 2020).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35087573", "locator": "sections[4] \"Differential Expression Analysis\" paragraph 2", "quote": "The R package “limma” (bioconductor) was performed to analyze the differentially expressed genes (DEGs) between the normal and high WSS groups (Smyth et al., 2005). The DEGs were screening out according to the following two cutoff criteria: adjusted p-value <0.05 and absolute log2 [fold change (FC)] >1 (Rougeot et al., 2019; Gao et al., 2020)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35087573", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The data sets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Limma analysis of GSE23289 identified 260 differentially expressed genes between the normal- and high-WSS groups.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "As a result, using the cutoff criteria (adjusted p-value <0.05 and |log2FC|>1), compared with the normal WSS groups, a total of 260 DEGs (121 upregulated and 139 downregulated genes) were identified in the high WSS groups, which provided the underlying clues to study atherogenesis and atherosclerotic progression (Supplementary Table 1)."}, "evidence": [{"asset": "source:pmid:35087573", "locator": "sections[11] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "As a result, using the cutoff criteria (adjusted p-value <0.05 and |log2FC|>1), compared with the normal WSS groups, a total of 260 DEGs (121 upregulated and 139 downregulated genes) were identified in the high WSS groups, which provided the underlying clues to study atherogenesis and atherosclerotic progression (Supplementary Table 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Limma analysis of GSE23289 identified 260 differentially expressed genes between the normal- and high-WSS groups.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35087573"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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