Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (6): 1082-1087. doi: 10.19723/j.issn.1671-167X.2020.06.015

Previous Articles     Next Articles

Association between CMTM5 gene and coronary artery disease and the relative mechanism

Teng-fei LIU,Tao LIN,Li-hui REN,Guang-ping LI,Jian-jun PENG()   

  1. Department of Cardiology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100034, China
  • Received:2018-12-13 Online:2020-12-18 Published:2020-12-13
  • Contact: Jian-jun PENG E-mail:pjj1972@sina.com
  • Supported by:
    Foundation of Research and Development Plan of China Railway Corporation(J2017Z608);Youth Foundation(2017-q27);Open Research Funding of Central Laboratory of Beijing Shijitan Hospital Affiliated to the Capital Medical University(2019-KF28)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells. Methods: Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells. Results: In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P<0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P<0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P<0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P<0.01). Conclusion: CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.

Key words: Atherosclerosis, Coronary artery disease, CMTM5, Gene

CLC Number: 

  • R543.3

Table 1

Baseline characteristics of the patients in CAD group and control group"

Variables Control group (n=350) CAD group (n=350) P
Age/years, x-±s 58.2±7.3 58.7±8.2 0.535
Gender/(male/female), n 200/150 200/150 Match
BMI/(kg/m2), x-±s 25.0±4.0 25.3±5.3 0.525
DM, n (%) 32 (9.1) 79 (22.6) <0.001*
Hypertension, n (%) 185 (52.9) 220 (62.9) 0.013*
Current smoking, n (%) 115 (32.9) 170 (48.6) <0.001*
TG/(mmol/L), x-±s 2.15±1.02 2.24±1.30 0.002*
TC/(mmol/L), x-±s 4.72±1.05 5.03±1.61 <0.001*
LDL-C/(mmol/L), x-±s 2.52±0.62 2.63±0.83 0.013*
HDL-C/(mmol/L), x-±s 1.41±0.44 1.44±0.53 0.286

Figure 1

CMTM5 mRNA expression and its plasma level between CAD group and control group A, CMTM5 mRNA expression in the two groups; B, plasma level of CMTM5 in the two groups. * P<0.05. CAD, coronary artery disease."

Table 2

Logistic regression analysis of coronary artery disease risk factors"

Risk factors B SE OR 95%CI P
Lower Upper
Age -0.960 0.116 0.383 0.305 0.481 <0.001
Gender 0.567 0.067 1.763 1.546 2.010 <0.001
BMI -0.007 0.008 0.993 0.976 0.971 0.377
Smoking -0.822 0.070 0.439 0.383 0.504 <0.001
Hypertension 0.350 0.066 1.420 1.247 1.617 <0.001
Diabetes mellitus 0.579 0.052 1.784 1.611 1.975 <0.001
Hyperlipidemia 0.259 0.070 1.296 1.130 1.487 <0.001
CMTM5 -0.044 0.007 0.957 0.943 0.971 0.002

Figure 2

Effects of CMTM5 gene expression changes on THP-1 adhesion to ECs (fluorescence staining ×4) **P<0.01. EN, non-infected ECs group; EO, CMTM5 overexpression ECs group; EO-MOCK, lenti-mock infected ECs group; ES, CMTM5 suppression ECs group; ES-MOCK, lenti-mock infected ECs group; HPF, high-power field."

Figure 3

Effects of CMTM5 gene expression changes on THP-1 migration to ECs(Giemsa staining ×10) ** P<0.01. Abbreviations as in Figure 2."

[1] Hansson GK. Inflammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med, 2005,352(16):1685-1695.
doi: 10.1056/NEJMra043430 pmid: 15843671
[2] Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options[J]. Nat Med, 2011,17(11):1410-1422.
doi: 10.1038/nm.2538 pmid: 22064431
[3] Aikawa M, Libby P. The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach[J]. Cardiovasc Pathol, 2004,13(3):125-138.
pmid: 15081469
[4] Koenen RR, Weber C. Chemokines: established and novel targets in atherosclerosis[J]. EMBO Mol Med, 2011,3(12):713-725.
doi: 10.1002/emmm.201100183
[5] Braunersreuther V, Mach F, Steffens S. The specific role of chemokines in atherosclerosis[J]. Thromb Haemost, 2007,97(5):714-721.
pmid: 17479181
[6] Zernecke A, Shagdarsuren E, Weber C. Chemokines in atherosclerosis: an update[J]. Arterioscler Thromb Vasc Biol, 2008,28(11):1897-1908.
doi: 10.1161/ATVBAHA.107.161174 pmid: 18566299
[7] Aukrust P, Halvorsen B, Yndestad A, et al. Chemokines and cardiovascular risk[J]. Arterioscler Thromb Vasc Biol, 2008,28(11):1909-1919.
doi: 10.1161/ATVBAHA.107.161240 pmid: 18669888
[8] Li H, Guo X, Shao L, et al. CMTM5-v1, a four-transmembrane protein, presents a secreted form released via a vesicle-mediated secretory pathway[J]. BMB Rep, 2010,43(3):182-187.
pmid: 20356458
[9] Voora D, Cyr D, Lucas J, et al. Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events[J]. J Am Coll Cardiol, 2013,62(14):1267-1276.
doi: 10.1016/j.jacc.2013.05.073 pmid: 23831034
[10] 刘滕飞, 张婧薇, 陈夏欢, 等. CMTM5基因rs723840单核苷酸多态性与阿司匹林治疗下血小板高反应性的相关性研究[J]. 北京大学学报(医学版), 2015,47(6):905-909.
doi: 10.3969/j.issn.1671-167X.2015.06.003
[11] Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation[J]. N Engl J Med, 2006,354(6):610-621.
doi: 10.1056/NEJMra052723 pmid: 16467548
[12] Heydtmann M, Adams DH. Chemokines in the immunopathogenesis of hepatitis C infection[J]. Hepatology, 2009,49(2):676-688.
doi: 10.1002/hep.22763 pmid: 19177577
[13] Golay J, Introna M. Chemokines and antagonists in non-Hodgkin’s lymphoma[J]. Expert Opin Ther Targets, 2008,12(5):621-635.
doi: 10.1517/14728222.12.5.621 pmid: 18410244
[14] Tiemessen CT, Kuhn L. CC chemokines and protective immunity: insights gained from mother-to-child transmission of HIV[J]. Nat Immunol, 2007,8(3):219-222.
doi: 10.1038/ni0307-219 pmid: 17304227
[15] Dhami H, Fritz CE, Gankin B, et al. The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies[J]. J Clin Pharm Ther, 2009,34(2):147-160.
doi: 10.1111/j.1365-2710.2008.00978.x pmid: 19250135
[16] Lundberg GA, Kellin A, Samnegard A, et al. Severity of coronary artery stenosis is associated with a polymorphism in the CXCL16/SR-PSOX gene[J]. J Intern Med, 2005,257(5):415-422.
doi: 10.1111/j.1365-2796.2005.01469.x pmid: 15836657
[17] Singh N, Rai H, Sinha N, et al. Association of V249I and T280M polymorphisms in the chemokine receptor CX3CR1 gene with early onset of coronary artery disease among North Indians[J]. Genet Test Mol Biomarkers, 2012,16(7):756-760.
doi: 10.1089/gtmb.2011.0256 pmid: 22731642
[18] Cai W, Tao J, Zhang X, et al. Contribution of homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 to coronary artery disease[J]. Arterioscler Thromb Vasc Biol, 2014,34(9):1933-1941.
pmid: 24990231
[19] Zhang JW, Liu TF, Chen XH, et al. Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function[J]. Gene, 2017,624:56-65.
doi: 10.1016/j.gene.2017.04.041
[1] Zhihui WU, Mingzhi HU, Qiaoying ZHAO, Fengfeng LV, Jingying ZHANG, Wei ZHANG, Yongfu WANG, Xiaolin SUN, Hui WANG. Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 860-867.
[2] Jun WANG, Lan YAO, Ning ZHANG, Libin SUO, Hongpei LI, Yue WEI, Peng CHA, Zheng LIANG, Kunpeng LIU. Effects of unilateral thoracic paravertebal block on hemodynamic and the level of conscionsness during double lumen endotracheal intubation [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 890-895.
[3] Jing HE,Zhongze FANG,Ying YANG,Jing LIU,Wenyao MA,Yong HUO,Wei GAO,Yangfeng WU,Gaoqiang XIE. Relationship between lipid metabolism molecules in plasma and carotid atheroscle-rotic plaques, traditional cardiovascular risk factors, and dietary factors [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 722-728.
[4] Huangda GUO,Hexiang PENG,Siyue WANG,Tianjiao HOU,Yixin LI,Hanyu ZHANG,Mengying WANG,Yiqun WU,Xueying QIN,Xun TANG,Jing LI,Dafang CHEN,Yonghua HU,Tao WU. A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study [J]. Journal of Peking University (Health Sciences), 2024, 56(3): 375-383.
[5] Han ZHAO,Yan WEI,Xuehui ZHANG,Xiaoping YANG,Qing CAI,Chengyun NING,Mingming XU,Wenwen LIU,Ying HUANG,Ying HE,Yaru GUO,Shengjie JIANG,Yunyang BAI,Yujia WU,Yusi GUO,Xiaona ZHENG,Wenjing LI,Xuliang DENG. Bionic design, preparation and clinical translation of oral hard tissue restorative materials [J]. Journal of Peking University (Health Sciences), 2024, 56(1): 4-8.
[6] Yuan PAN,Hang GU,Han XIAO,Lijun ZHAO,Yiman TANG,Wenshu GE. Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells [J]. Journal of Peking University (Health Sciences), 2024, 56(1): 9-16.
[7] Xiaoqiang LIU,Yin ZHOU. Risk factors of perioperative hypertension in dental implant surgeries with bone augmentation [J]. Journal of Peking University (Health Sciences), 2024, 56(1): 93-98.
[8] Deng-hui DUAN,Hom-Lay WANG,En-bo WANG. Role of collagen membrane in modified guided bone regeneration surgery using buccal punch flap approach: A retrospective and radiographical cohort study [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1097-1104.
[9] Huan-rui LIU,Xiang PENG,Sen-lin LI,Xin GOU. Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment [J]. Journal of Peking University (Health Sciences), 2023, 55(5): 793-801.
[10] Yin-ji JIN,Lin SUN,Jin-xia ZHAO,Xiang-yuan LIU. Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 631-635.
[11] Shang XIE,Zhi-gang CAI,Xiao-feng SHAN. Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 697-701.
[12] Yun-fei DAI,He LIU,Chu-fang PENG,Xi-jun JIANG. Retrospective evaluation of treatment outcomes in immature teeth treated with regenerative endodontic procedures with an over-36-month review [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 729-735.
[13] Yuan-yuan XU,Zhi-lin SUN,Xiu-lian ZHANG,Zi-lian LIU,Wei LIU,Xin GUAN. Carbamazepine induced Stevens-Johnson syndrome in Han Chinese with positive HLA-A * 3101 gene: A case report [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 755-757.
[14] Xue-heng WANG,Si-yue WANG,He-xiang PENG,Meng FAN,Huang-da GUO,Tian-jiao HOU,Meng-ying WANG,Yi-qun WU,Xue-ying QIN,Xun TANG,Jin LI,Da-fang CHEN,Yong-hua HU,Tao WU. Genotype-environment interaction on arterial stiffness: A pedigree-based study [J]. Journal of Peking University (Health Sciences), 2023, 55(3): 400-407.
[15] Yun-fei SHI,Hao-jie WANG,Wei-ping LIU,Lan MI,Meng-ping LONG,Yan-fei LIU,Yu-mei LAI,Li-xin ZHOU,Xin-ting DIAO,Xiang-hong LI. Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma [J]. Journal of Peking University (Health Sciences), 2023, 55(3): 521-529.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd