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

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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)

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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."

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