Aims: To investigate the differentially expressed genes (DEGs) and molecular interaction in unstable atherosclerotic carotid plaques.
Methods: Gene expression datasets GSE41571, GSE118481, and E-MTAB-2055 were analyzed. Co-regulated DEGs in at least two datasets were analyzed with the enrichment of Gene Ontology Biological Process (GO-BP), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) networks, interrelationships between miRNAs/transcriptional factors, and their target genes and drug–gene interactions. The expression of notable DEGs in human carotid artery plaques and plasma was further identified.
Results: The GO-BP enrichment analysis revealed that genes associated with inflammatory response, and extracellular matrix organization were altered. The KEGG enrichment analysis revealed that upregulated DEGs were enriched in the tuberculous, lysosomal, and chemokine signaling pathways, whereas downregulated genes were enriched in the focal adhesion and PI3K/Akt signaling pathway. Collagen type I alpha 2 chain (COL1A2), adenylate cyclase 3 (ADCY3), C-X-C motif chemokine receptor 4 (CXCR4), and TYRO protein tyrosine kinase binding protein (TYROBP) might play crucial roles in the PPI networks. In drug–gene interactions, colonystimulating factor-1 receptor had the most drug interactions. Insulin-like growth factor binding protein 6 (IGFBP6) was markedly downregulated in unstable human carotid plaques and plasma. Under a receiver operating characteristic curve analysis, plasma IGFBP6 had a significant discriminatory power (AUC, 0.894; 95% CI, 0.810–0.977), with a cutoff value of 142.08 ng/mL.
Conclusions: The genes COL1A2, ADCY3, CXCR4, and TYROBP are promising targets for the prevention of unstable carotid plaque formation. IGFBP6 may be an important biomarker for predicting vulnerable plaques.
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410004222630160643","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410316582"}],"foaf:name":[{"@language":"en","@value":"Liu Yandong"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Second Military Medical University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222630160641","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410316583"}],"foaf:name":[{"@language":"en","@value":"Huan Wei"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Second Military Medical University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222630160640","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410316585"}],"foaf:name":[{"@language":"en","@value":"Zou Sili"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Second Military Medical University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222630160642","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410316584"}],"foaf:name":[{"@language":"en","@value":"Wu Jianjin"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Second Military Medical University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410004222630160644","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000410316586"}],"foaf:name":[{"@language":"en","@value":"Qu Lefeng"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Second Military Medical University"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13403478"},{"@type":"EISSN","@value":"18803873"}],"prism:publicationName":[{"@language":"en","@value":"Journal of Atherosclerosis and Thrombosis"},{"@language":"ja","@value":"Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ"},{"@language":"en","@value":"JAT"},{"@language":"en","@value":"J Atheroscler Thromb"},{"@language":"ja","@value":"Ｊ Ａｔｈｅｒｏｓｃｌｅｒ Ｔｈｒｏｍｂ"}],"dc:publisher":[{"@language":"en","@value":"Japan Atherosclerosis Society"},{"@language":"ja","@value":"一般社団法人 日本動脈硬化学会"}],"prism:publicationDate":"2020-10-01","prism:volume":"27","prism:number":"10","prism:startingPage":"1068","prism:endingPage":"1085"},"reviewed":"false","url":[{"@id":"https://www.jstage.jst.go.jp/article/jat/27/10/27_52993/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2021183227"}],"availableAt":"2020-10-01","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Atherosclerosis","dc:title":"Atherosclerosis"},{"@id":"https://cir.nii.ac.jp/all?q=Cerebrovascular%20stroke","dc:title":"Cerebrovascular stroke"},{"@id":"https://cir.nii.ac.jp/all?q=Carotid%20stenosis","dc:title":"Carotid stenosis"},{"@id":"https://cir.nii.ac.jp/all?q=Pathway%20analysis","dc:title":"Pathway analysis"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20transduction","dc:title":"Signal transduction"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20expression","dc:title":"Gene expression"},{"@id":"https://cir.nii.ac.jp/all?q=Insulin-like%20growth%20factor%20binding%20protein%206","dc:title":"Insulin-like growth factor binding protein 6"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011146367678848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Oxidized low-density lipoprotein (oxLDL) supports Mycobacterium tuberculosis survival in macrophages by inducing lysosomal dysfunction"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011146394726016","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Monocyte-Macrophages and T Cells in Atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292274168463744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"DGIdb 2.0: mining clinically relevant drug–gene interactions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617908863616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"WebGestalt: an integrated system for exploring gene sets in various biological contexts"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617912258944","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"KEGG: Kyoto Encyclopedia of Genes and Genomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617916331648","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A comparison of normalization methods for high density\noligonucleotide array data based on variance and bias"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619042855168","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Liraglutide reduces body weight by upregulation of adenylate cyclase 3"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619096211072","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574092883508352","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Gene Ontology: tool for the unification of biology"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855567863980544","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"affy—analysis of Affymetrix GeneChip data at the probe level"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855567865731072","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855567868890752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569430697728","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"DAP10‐ and DAP12‐associated receptors in innate immunity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569525830912","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570640712832","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Galectin-1 Restricts Vascular Smooth Muscle Cell Motility Via Modulating Adhesion Force and Focal Adhesion Dynamics"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571498257664","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Progress and challenges in translating the biology of atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137046272744704","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418521215598080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Macrophages in vascular inflammation and atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699993567310592","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699994030049024","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Defective Autophagy in Atherosclerosis: To Die or to Senesce?"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699995615864064","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699995856975360","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981470288165376","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471112163072","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Unusual genetic variants associated with hypercholesterolemia in Argentina"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471202706176","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Elevated plasma YKL‐40 levels and ischemic stroke in the general population"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943375561472","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Correction: Corrigendum: Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262945684459136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544420096367360","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TFEB and trehalose drive the macrophage autophagy-lysosome system to protect against atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544420625080960","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544420793580032","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Diabetic retinopathy is associated with decreased serum levels of free IGF-I and changes of IGF-binding proteins"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825893749056768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Smooth Muscle Enriched Long Noncoding RNA (\n SMILR\n ) Regulates Cell Proliferation"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894321993216","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The CXCL12/CXCR4 chemokine ligand/receptor axis in cardiovascular disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894901353600","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895822999424","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Overexpression of YKL-40 Predicts Plaque Instability in Carotid Atherosclerosis with CagA-Positive Helicobacter Pylori Infection"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895869020672","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Screening of potential gene markers for predicting carotid atheroma plaque formation using bioinformatics approaches"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368477901952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368520228736","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368886394880","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chronic miR‐29 antagonism promotes favorable plaque remodeling in atherosclerotic mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107369141239040","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"COLLAGENS: Molecular Biology, Diseases, and Potentials for Therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370400861696","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370607906816","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370947383552","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cholesterol, inflammation and innate immunity"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845024480768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Histological Correlates of Carotid Plaque Surface Morphology on Lumen Contrast Imaging"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845153424768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Intervene: a tool for intersection and visualization of multiple gene or genomic region sets"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845535037056","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Evidence for Rapid Accumulation and Persistently Disordered Architecture of Fibrillar Collagen in Human Coronary Restenosis Lesions * *This study was supported by a grant from the Medical Research Council of Canada (MT-11715)"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845693550848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795775473152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233268828304384","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Stroke Data Bank: design, methods, and baseline characteristics."}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680449561856","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Identification by microarray technology of key genes involved in the progression of carotid atherosclerotic plaque"}]},{"@id":"https://cir.nii.ac.jp/crid/1390283659837296896","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Clinical Impact of Carotid Plaque Score rather than Carotid Intima-Media Thickness on Recurrence of Atherosclerotic Cardiovascular Disease Events"}]},{"@id":"https://cir.nii.ac.jp/crid/1390564238102939904","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Investigation of the Underlying Genes and Mechanism of Macrophage-Enriched Ruptured Atherosclerotic Plaques Using Bioinformatics Method"}]},{"@id":"https://cir.nii.ac.jp/crid/1390845713026201728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Relationship between CCL22 Expression by Vascular Smooth Muscle Cells and Macrophage Histamine Receptors in Atherosclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1390845713054935936","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Identification of Metabolites Associated with Onset of CAD in Diabetic Patients Using CE-MS Analysis: A Pilot Study"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2008064654"},{"@type":"CROSSREF","@value":"10.5551/jat.52993"},{"@type":"PUBMED","@value":"32037372"},{"@type":"CIA","@value":"130007920601"}]}