Analysis of potential mechanisms of below-the-knee atherosclerosis obliteran based on weighted correlation network analysis and immune infiltration
Author:
Affiliation:

1.Department of Clinical Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, China;2.Department of Peripheral Vascular Disease, Jinan Municipal Hospital of Traditional Chinese Medicine, Jinan, Shandong 250012, China)

Clc Number:

R5

  • Article
  • | |
  • Metrics
  • |
  • Reference [37]
  • |
  • Related [20]
  • | | |
  • Comments
    Abstract:

    Aim To investigate the potential mechanisms and immunological correlation of below-the-knee atherosclerosis obliteran (BTK). Methods The GSE100927 dataset was downloaded from the Gene Expression Omnibus.Differentially expressed genes of BTK were screened by using “limma” package of the R and weighted correlation network analysis (WGCNA). Signaling pathway enrichment analysis was performed by “clusterProfiler” package of the R. The protein-protein interaction network was constructed, and the core genes associated with BTK were screened. The differences of the core genes’ expression between the BTK samples and normal samples were analyzed, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the core genes. The CIBERSORT was used to evaluate the distribution of immune cells in each sample and to calculate the differences between the BTK samples and normal samples. Results 153 genes were up-regulated and 63 genes were down-regulated in BTK. WGCNA results indicated that the differential expression genes in BTK were mainly up-regulated, involving signaling pathways such as cholesterol metabolism and platelet activation; protein tyrosine phosphatase receptor type C (PTPRC), Spi-1 proto-oncogene (SPI1),colony stimulating factor 1 receptor (CSF1R), and Fc gamma receptor Ⅲa (FCGR3A) were probably the core genes in BTK, which have good diagnostic efficacy. BTK was positively correlated with the degree of infiltration of monocytes (r=0.419, P=0.037) and negatively correlated with the degree of infiltration of M2 macrophages (r=-0.491, P=0.013). Conclusion The BTK involved various signaling pathways such as cholesterol metabolism and platelet activation and was closely related to monocyte- and macrophage-mediated immune responses. PTPRC, SPI1, CSF1R, and FCGR3A may be the core genes of BTK.

    Reference
    [1] SONG P G, RUDAN D N, WANG M L, et al.National and subnational estimation of the prevalence of peripheral artery disease (PAD) in China:a systematic review and Meta-analysis.J Glob Health, 9,9(1):010601.
    [2] 包俊敏, 刘冰, 沈晨阳, 等.股腘动脉闭塞症的诊断和治疗中国专家共识.中国循环杂志, 2,7(7):669-676.BAO J M, LIU B, SHEN C Y, et al.Chinese expert consensus on the diagnosis and treatment of femoral-popliteal artery occlusive disease.Chin Circ J, 2,7(7):669-676.
    [3] FERRARESI R, CLERICI G, CASINI A, et al.Foot angiosomes:instructions for use.Int J Low Extrem Wounds, 0,9(4):293-304.
    [4] FUKAGAWA T, MORI S, YAMAWAKI M, et al.Prediction of wound recurrence in patients with chronic limb-threatening ischemia undergoing endovascular treatment.J Endovasc Ther, 2022.DOI:10.1177/15266028221098702.
    [5] 刘文导, 冯柳迁, 孟凡喆, 等.下肢动脉硬化闭塞症介入治疗效果及影响术后复发因素分析.介入放射学杂志, 7,6(6):514-517.LIU W D, FENG L Q, MENG F Z, et al.Curative effect of interventional therapy for arteriosclerosis obliterans of lower extremity and analysis of recurrence factors.J Interventional Radiol, 7,6(6):514-517.
    [6] 吴章, 马鲁波, 吴玉泉, 等.双向入路治疗下肢动脉远端流出道闭塞性病变.介入放射学杂志, 0,9(7):707-710.WU Z, MA L B, WU Y Q, et al.The application of bidirectional approach technique in interventional treatment of occlusive lesion of distal outflow tract of lower extremity artery.J Interventional Radiol, 0,9(7):707-710.
    [7] 王子豪, 胡何节, 方征东, 等.外周血免疫及炎性指标与下肢动脉硬化严重程度相关性分析.血管与腔内血管外科杂志, 0,6(2):103-107.WANG ZI H, HU H J, FANG Z D, et al.Correlation analysis of peripheral blood immune and inflammatory indexes with the severity of lower extremity atherosclerosis.J Vasc Endovasc Surg, 0,6(2):103-107.
    [8] CHICCO D.Gene expression from GEO:an R package to facilitate data reading from gene expression omnibus(GEO).Methods Mol Biol, 2,1:187-194.
    [9] LIU S, WANG Z, ZHU R, et al.Three differential expression analysis methods for RNA sequencing:limma, EdgeR, DESeq2.J Vis Exp, 2021.DOI:10.3791/62528.
    [10] LANGFELDER P, HORVATH S W.WGCNA:an R package for weighted correlation network analysis.BMC Bioinformatics, 8,9:559.
    [11] YU G A, WANG L G, HAN Y Y, et al.Cluster profiler:an R package for comparing biological themes among gene clusters.OMICS, 2,6(5):284-287.
    [12] SZKLARCZYK D, GABLE A L, NASTOU K C, et al.The STRING database in 2021:customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.Nucleic Acids Res, 1,9(D1):D605-D612.
    [13] CHIN C H, CHEN S H, WU H H, et al.cytoHubba:identifying hub objects and sub-networks from complex interactome.BMC Syst Biol, 4,8 Suppl 4(Suppl 4):S11.
    [14] CHEN B, KHODADOUST M S, LIU C L, et al.Profiling tumor infiltrating immune cells with CIBERSORT.Methods Mol Biol, 8,1:243-259.
    [15] NIE H, YAN C, ZHOU W, et al.Analysis of immune and inflammation characteristics of atherosclerosis from different sample sources.Oxid Med Cell Longev, 2,2:5491038.
    [16] 彭进.ATF3在动脉粥样硬化病变演进中的作用及其机制研究.贵阳:贵州医科大学, 2021.PENG J.Research on the role and mechanism of ATF3 in the progression of atherosclerosis.Guiyang:Guizhou Medical University, 2021.
    [17] 王玉, 孙晓宇, 罗亚, 等.冠状动脉粥样斑块内CD45表达水平与病灶结构变化的关系.中国动脉硬化杂志, 9,7(2):114-119.WANG Y, SUN X Y, LUO Y, et al.CD45 expression level in coronary atherosclerotic plaques and its relationship to lesion structure changes.Chin J Arterioscler, 9,7(2):114-119.
    [18] DI GREGOLI K, JOHNSON J L.Role of colony-stimulating factors in atherosclerosis.Curr Opin Lipidol, 2,3(5):412-421.
    [19] WEI Y, ZHU M, CORBALN-CAMPOS J, et al.Regulation of CSF1R and Bcl6 in macrophages mediates the stage-specific effects of microRNA-155 on atherosclerosis.Arterioscler Thromb Vasc Biol, 5,5(4):796-803.
    [20] HUANG Y, YIN H J, WANG J S, et al.Aberrant expression of FcγRⅢA (CD16) contributes to the development of atherosclerosis.Gene, 2,8(1):91-95.
    [21] DURAN E K, PRADHAN A D.Triglyceride-rich lipoprotein remnants and cardiovascular disease.Clin Chem, 1,7(1):183-196.
    [22] 何清清, 包宇实.血小板受体信号在血栓炎症相关疾病中作用研究进展.中华实用诊断与治疗杂志, 1,5(11):1185-1188.HE Q Q, BAO Y S.Role of platelet receptor signaling in thromboinflammatory diseases.J Chin Pract Diagn Ther, 1,5(11):1185-1188.
    [23] MARTINOD K, DEPPERMANN C.Immunothrombosis and thromboinflammation in host defense and disease.Platelets, 1,2(3):314-324.
    [24] 王克华, 王金, 王磊, 等.circRNA SKA3通过miR-1303调控TLR4轴在动脉粥样硬化中的作用[J/OL].中国动脉硬化杂志, 2023:1-23[2023-04-11].http://kns.cnki.net/kcms/detail/43.1262.R.20230411.1543.002.html.WANG K H, WANG J, WANG L, et al.circRNA SKA3 regulates the role of TLR4 axis in atherosclerosis through miR-1303.Chin J Arterioscler, 2023:1-23[2023-04-11].http://kns.cnki.net/kcms/detail/43.1262.R.20230411.1543.002.html.
    [25] 苏波, 杨咏梅, 刘政海, 等.Adiporedoxin抑制TNF-α诱导的血管内皮细胞与单核细胞粘附.中国药理学通报, 1,7(2):295-296.SU B, YANG Y M, LIU Z H, et al.Adiporedoxin inhibits adhesion of TNF-α induced vascular endothelial cells to monocytes.Chin Pharmacol Bull, 1,7(2):295-296.
    [26] YANG X L, JIA J, YU Z, et al.Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit.BMC Cardiovasc Disord, 0,0(1):133.
    [27] 刘平, 崔公让.不同程度颈动脉粥样硬化老年患者T淋巴细胞分化亚群、炎症水平与血管内皮功能关联性分析.免疫学杂志, 0,6(11):976-983.LIU P, CUI G R.Association of T lymphocyte differentiation subgroups and inflammation levels with vascular endothelial function in elderly patients with different degrees of carotid atherosclerosis.Immunol J, 0,6(11):976-983.
    [28] HE X, LIANG B, GU N.Th17/Treg imbalance and atherosclerosis.Dis Markers, 0,0:8821029.
    [29] 尹丽梅, 袁建, 陈楷, 等.解毒活血方调控PI3K/Akt/mTOR信号通路对ApoE-/-动脉粥样硬化小鼠斑块稳定性的影响.中国实验方剂学杂志, 3,9(12):112-120.YIN L M, YUAN J, CHEN K, et al.Jiedu Huoxue prescription modulating PI3K/Akt/mTOR signaling pathway on plaque stability in ApoE-/- As mice.Chin J Exp Tradit Med Form, 3,9(12):112-120.
    [30] 谭丽萍, 韩凤珍, 胥明霞.马齿苋多糖调节PPARγ/NF-κB通路对大鼠动脉粥样硬化斑块形成的影响.河北医药, 3,5(3):330-334.TAN L P, HAN F Z, XU M X.Effects of portulaca polysaccharide on atherosclerotic plaque in rats by regulating PPARγ/NFκB pathway.Hebei Med J, 3,5(3):330-334.
    [31] 何欣, 顾宁.免疫细胞与动脉粥样硬化斑块研究进展.中国动脉硬化杂志, 1,9(7):629-634.HE X, GU N.The research progress between immune cells and atherosclerotic plaques.Chin J Arterioscler, 1,9(7):629-634.
    [32] 徐芳芷, 窦琳, 沈涛, 等.免疫细胞在动脉粥样硬化中的代谢重编程现象.中国动脉硬化杂志, 3,1(3):218-224.XU F Z, DOU L, SHEN T, et al.Metabolic reprogramming of immune cells in atherosclerosis.Chin J Arterioscler, 3,1(3):218-224.
    [33] NEWMAN A M, LIU C L, GREEN M R, et al.Robust enumeration of cell subsets from tissue expression profiles.Nat Methods, 5,2(5):453-457.
    [34] BCK M, YURDAGUL A J, TABAS I, et al.Inflammation and its resolution in atherosclerosis:mediators and therapeutic opportunities.Nat Rev Cardiol, 9,6(7):389-406.
    [35] 刘继军, 于林君, 王博, 等.沙格列汀激活AMPK-PPARα途径促进巨噬细胞向M2型极化减轻动脉粥样硬化的作用研究.实用药物与临床, 2,5(4):295-301.LIU J J, YU L J, WANG B, et al.Saxagliptin activating the AMPK-PPAR α pathway to promote M2 polarization of macrophages to reduce atherosclerosis.Pract Pharm Clin Remed, 2,5(4):295-301.
    [36] LIBBY P, HANSSON G K.From focal lipid storage to systemic inflammation:JACC review topic of the week.J Am Coll Cardiol, 9,4(12):1594-1607.
    [37] 姚海鹏, 钱勇江, 王中群.基于单细胞转录组鉴定动脉粥样硬化自身免疫表征.中国动脉硬化杂志, 2,0(10):852-860.YAO H P, QIAN Y J, WANG Z Q.Identification of autoimmune characterization of atherosclerosis based on single cell transcriptome.Chin J Arterioscler, 2,0(10):852-860.
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

LI Jian, WANG Yutao, WANG Shixin. Analysis of potential mechanisms of below-the-knee atherosclerosis obliteran based on weighted correlation network analysis and immune infiltration[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2023,31(8):677-686.

Copy
Share
Article Metrics
  • Abstract:327
  • PDF: 886
  • HTML: 0
  • Cited by: 0
History
  • Received:November 09,2022
  • Revised:May 04,2023
  • Online: July 20,2023
Article QR Code