Identification of Biomarkers of Autophagy-Related Genes Between Early and Advanced Carotid Atherosclerosis

Background Accumulating evidence demonstrates that autophagy is important in inhibiting inflammation and cholesterol efflux. It suggested the autophagy may be a treatment of atherosclerosis. Thus, we screened autophagy-related mRNA to explore their mechanism of scientific basis for early diagnosis and therapy of atherosclerosis. Methods The GSE28829 datasets were assessed to analyze differentially expressed genes by GEO2R. And autophagy-related hub genes were identified by HADb. The biological function of autophagy-related DEmRNAs was examined by Metascape. The construction of a protein–protein network was explored by String. Cytohubba was utilized to screen hub genes. Analysis of DEmiRNA-mRNA pairs was executed by DIANA microT-CDS database. Finally, correlation analysis was carried out to identify the relationship between DEARGs and clinical and prognostic factors. Results A number of 1087 DEGs and 19 autophagy-related DEmRNAs were identified in advanced carotid atherosclerotic plaque compared with the early. The biological function containing development and growth was enriched. Moreover, we screened the top hub nodes with the highest degrees. MicroRNAs (miRNAs) are confirmed to participate in genesis and progression of atherosclerosis, so we further analyzed the miRNA–mRNA regulatory network genes with four hub genes to explore their potential mechanism in atherosclerosis. Then, we revealed co-expression of four key genes CTSB, ITGB1, CXCR4, TNFSF10 and autophagy-related genes. As for the clinical factors, hypertension factor showed higher expression of ITGB1. The probability of coronary heart disease factor was significantly increased with high expression of CTSB and CXCR4, as well as low expression of ITGB1 and TNFSF10. Diabetes factor tended to express distinguished levels of CTSB and ITGB1. TNFSF10 was highly expressed in both hyperlipidemia and ischemic stroke factor. Conclusion CTSB, ITGB1, CXCR4 and TNFSF10 may be critical in atherosclerosis development and were thought to be potential diagnostic biomarkers for atherosclerosis.

[1]  M. Zhang,et al.  K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques , 2021, Cardiovascular Drugs and Therapy.

[2]  Yuan Zhang,et al.  Combined Analysis of Surface Protein Profile and microRNA Expression Profile of Exosomes Derived from Brain Microvascular Endothelial Cells in Early Cerebral Ischemia , 2021, ACS omega.

[3]  N. Nighoghossian,et al.  A narrative review of the pathophysiology of ischemic stroke in carotid plaques: a distinction versus a compromise between hemodynamic and embolic mechanism , 2021, Annals of translational medicine.

[4]  F. Zhou,et al.  Identification of Potential Key Genes Involved in the Carotid Atherosclerosis , 2021, Clinical interventions in aging.

[5]  Y. Yue,et al.  HMGB1 downregulation in retinal pigment epithelial cells protects against diabetic retinopathy through the autophagy-lysosome pathway , 2021, Autophagy.

[6]  Yan-ni Yu,et al.  Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death , 2021, BMC Cardiovascular Disorders.

[7]  P. Lei,et al.  Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications , 2021, Medicinal research reviews.

[8]  C. Zhang,et al.  Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3 , 2021, Theranostics.

[9]  B. Dong,et al.  High Burden of Carotid Atherosclerosis in Rural Northeast China: A Population-Based Study , 2021, Frontiers in Neurology.

[10]  R. Lichtinghagen,et al.  Distinct systemic cytokine networks in symptomatic and asymptomatic carotid stenosis , 2020, Scientific Reports.

[11]  Xiaoqin Xia,et al.  Integrative Transcriptomic Analysis Reveals the Immune Mechanism for a CyHV-3-Resistant Common Carp Strain , 2020, bioRxiv.

[12]  Xiaoyan Zhu,et al.  Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis , 2020, Oxidative medicine and cellular longevity.

[13]  Filippo Cademartiri,et al.  Insight from imaging on plaque vulnerability: similarities and differences between coronary and carotid arteries-implications for systemic therapies. , 2020, Cardiovascular diagnosis and therapy.

[14]  Ajay Gupta,et al.  Brain imaging biomarkers of carotid artery disease , 2020, Annals of translational medicine.

[15]  A. Feuchtinger,et al.  Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis , 2020, bioRxiv.

[16]  Chao-qun Xu,et al.  Efficient Treatment of Atherosclerosis by Dexamethasone Acetate and Rapamycin Co-Loaded mPEG-DSPE Calcium Phosphate Nanoparticles. , 2020, Journal of biomedical nanotechnology.

[17]  M. Wintermark,et al.  Carotid plaque imaging and the risk of atherosclerotic cardiovascular disease. , 2020, Cardiovascular diagnosis and therapy.

[18]  T. Hashimoto,et al.  Essential autophagic protein Beclin 1 localizes to atherosclerotic lesions of human carotid and major intracranial arteries , 2020, Journal of the Neurological Sciences.

[19]  T. Wijeratne,et al.  Carotid artery stenosis and inflammatory biomarkers: the role of inflammation-induced immunological responses affecting the vascular systems , 2020, Annals of translational medicine.

[20]  Jia-wei Tian,et al.  Functional lncRNA-miRNA-mRNA networks in rabbit carotid atherosclerosis , 2020, Aging.

[21]  S. Zou,et al.  IGFBP6 Is Downregulated in Unstable Carotid Atherosclerotic Plaques According to an Integrated Bioinformatics Analysis and Experimental Verification , 2020, Journal of atherosclerosis and thrombosis.

[22]  M. Alirezaei,et al.  A food-responsive switch modulates TFEB and autophagy, and determines susceptibility to coxsackievirus infection and pancreatitis , 2020, Autophagy.

[23]  Jie Wang,et al.  Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease. , 2019, Journal of molecular and cellular cardiology.

[24]  M. Orho-Melander,et al.  sTRAIL-R2 (Soluble TNF [Tumor Necrosis Factor]-Related Apoptosis-Inducing Ligand Receptor 2) a Marker of Plaque Cell Apoptosis and Cardiovascular Events. , 2019, Stroke.

[25]  Ben He,et al.  Sulindac‐derived retinoid X receptor‐α modulator attenuates atherosclerotic plaque progression and destabilization in ApoE−/− mice , 2019, British journal of pharmacology.

[26]  E. Ng,et al.  Imaging modalities to diagnose carotid artery stenosis: progress and prospect , 2019, Biomedical engineering online.

[27]  D. Russell,et al.  Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study , 2019, BMC Neurology.

[28]  Jinzhen Wu,et al.  Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease , 2019, Aging.

[29]  Damian Szklarczyk,et al.  STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets , 2018, Nucleic Acids Res..

[30]  M. Hayakawa,et al.  Noninvasive Assessment of Stenotic Severity and Plaque Characteristics by Coronary CT Angiography in Patients Scheduled for Carotid Artery Revascularization , 2018, Journal of atherosclerosis and thrombosis.

[31]  S. Volpato,et al.  Relationship between low levels of circulating TRAIL and atheromatosis progression in patients with chronic kidney disease , 2018, PloS one.

[32]  André V Cordeiro,et al.  The role of cathepsin B in autophagy during obesity: A systematic review , 2018, Life sciences.

[33]  X. Yuan,et al.  Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq. , 2018, American journal of translational research.

[34]  Yunfeng Shan,et al.  Identification of key genes and miRNAs associated with carotid atherosclerosis based on mRNA-seq data , 2018, Medicine.

[35]  Yanxin Zhao,et al.  Gene expression profile analysis of the progression of carotid atherosclerotic plaques , 2018, Molecular medicine reports.

[36]  K. Vandenbroeck,et al.  Inflammation in human carotid atheroma plaques. , 2018, Cytokine & growth factor reviews.

[37]  S. Grundmann,et al.  MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy , 2017, Circulation research.

[38]  Valérie Metzinger-Le Meuth,et al.  The Involvement of miRNA in Carotid-Related Stroke , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[39]  J. Gillard,et al.  Imaging Carotid Atherosclerosis Plaque Ulceration: Comparison of Advanced Imaging Modalities and Recent Developments , 2017, American Journal of Neuroradiology.

[40]  W. Bojara,et al.  Early Diagnosis and Treatment of Coronary Heart Disease in Asymptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound) and Risk Factors , 2017, Cardiology research.

[41]  W. Bojara,et al.  Early Diagnosis and Treatment of Coronary Heart Disease in Symptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound) , 2017, Cardiology research.

[42]  K. Vandenbroeck,et al.  A role for autophagy in carotid atherosclerosis , 2016, European stroke journal.

[43]  Ping Zhang,et al.  Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques , 2015, Journal of geriatric cardiology : JGC.

[44]  P. Camici,et al.  Markers of Inflammation Associated with Plaque Progression and Instability in Patients with Carotid Atherosclerosis , 2015, Mediators of inflammation.

[45]  Yongjun Cao,et al.  Autophagy in Atherosclerosis: A Phenomenon Found in Human Carotid Atherosclerotic Plaques , 2015, Chinese medical journal.

[46]  Chung-Yen Lin,et al.  cytoHubba: identifying hub objects and sub-networks from complex interactome , 2014, BMC Systems Biology.

[47]  Jeffrey A. Thompson,et al.  Common features of microRNA target prediction tools , 2014, Front. Genet..

[48]  N. Jain,et al.  Association of Carotid Plaque Echogenicity with Recurrence of Ischemic Stroke , 2013, North American journal of medical sciences.

[49]  J. Debnath,et al.  IκB kinase complex (IKK) triggers detachment-induced autophagy in mammary epithelial cells independently of the PI3K-AKT-MTORC1 pathway , 2013, Autophagy.

[50]  E. Mathiesen,et al.  The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromsø study , 2012, Cardiovascular Diabetology.

[51]  M. Daemen,et al.  Auto-Antigenic Protein-DNA Complexes Stimulate Plasmacytoid Dendritic Cells to Promote Atherosclerosis , 2012, Circulation.

[52]  H. Koyama,et al.  Association of serum TRAIL levels with atherosclerosis in patients with type 2 diabetes mellitus. , 2011, Diabetes research and clinical practice.

[53]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[54]  E. Chaikof,et al.  Pathogen-Sensing Plasmacytoid Dendritic Cells Stimulate Cytotoxic T-Cell Function in the Atherosclerotic Plaque Through Interferon-&agr; , 2006, Circulation.