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The relation of circulating cell division cycle 42 expression with Th1, Th2, and Th17 cells, adhesion molecules, and biochemical indexes in coronary heart disease patients

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Abstract

Background

Cell division cycle 42 (CDC42) regulates macrophage polarization, vascular inflammation, atherosclerosis progression, and modifies differentiation of T helper (Th) cells, while its potential as a biomarker in coronary heart disease (CHD) patients is still lacking. This study aimed to evaluate CDC42 expression, its correlation with Th1, Th2, and Th17 cells, adhesion molecules, and biochemical indexes in CHD patients.

Methods

One hundred two CHD patients and 50 controls were enrolled. CDC42 expression in peripheral blood mononuclear cells was assessed by reverse transcription quantitative polymerase chain reaction in all participants. In CHD patients, Th1, Th2, and Th17 cells were detected by flow cytometric analysis; meanwhile, serum levels of inflammatory cytokines and adhesion molecules were detected by enzyme-linked immunosorbent assay.

Results

CDC42 was lower in CHD patients (median (interquartile range (IQR)) = 0.431 (0.304–0.722)) than in controls (median (IQR) = 0.985 (0.572–1.760)) (p < 0.001). CDC42 was positively associated with Th2 cells (p = 0.016) and interleukin (IL)-10 (p = 0.034), but negatively correlated with Th17 cells (p < 0.001) and IL-17A (p < 0.001) in CHD patients. However, no association was found in CDC42 with Th1 cells (p = 0.199) or interferon-γ (p = 0.367) in CHD patients. Besides, CDC42 was negatively correlated with vascular cell adhesion molecule-1 (p = 0.013) and intercellular cell adhesion molecule-1 (p = 0.001) in CHD patients. Additionally, CDC42 negatively associated with C-reactive protein (p < 0.001), Gensini score (p < 0.001), total cholesterol (p = 0.039), and low-density lipoprotein cholesterol (p = 0.014), but not with other biochemical indexes (p > 0.05) in CHD patients.

Conclusion

CDC42 correlates with Th2 cells, Th17 cells, and adhesion molecules, also reflects inflammation, coronary stenosis degree, and cholesterol level in CHD patients.

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References

  1. Malakar AK, Choudhury D, Halder B et al (2019) A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 234(10):16812–16823. https://doi.org/10.1002/jcp.28350

    Article  CAS  PubMed  Google Scholar 

  2. Bauersachs R, Zeymer U, Briere JB et al (2019) Burden of coronary artery disease and peripheral artery disease: a literature review. Cardiovasc Ther 2019:8295054. https://doi.org/10.1155/2019/8295054

    Article  PubMed  PubMed Central  Google Scholar 

  3. Matsuzawa Y, Lerman A (2014) Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coron Artery Dis 25(8):713–724. https://doi.org/10.1097/MCA.0000000000000178

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wong D, Turner AW, Miller CL (2019) Genetic insights into smooth muscle cell contributions to coronary artery disease. Arterioscler Thromb Vasc Biol 39(6):1006–1017. https://doi.org/10.1161/ATVBAHA.119.312141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Houston M (2018) The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease. Ther Adv Cardiovasc Dis 12(3):85–108. https://doi.org/10.1177/1753944717743920

    Article  PubMed  PubMed Central  Google Scholar 

  6. Behnes M, Fastner C, Ansari U et al (2015) New oral anticoagulants in coronary artery disease. Cardiovasc Hematol Disord Drug Targets 15(2):101–105. https://doi.org/10.2174/1871529x1502151209111429

    Article  CAS  PubMed  Google Scholar 

  7. Leigh JA, Alvarez M, Rodriguez CJ (2016) Ethnic minorities and coronary heart disease: an update and future directions. Curr Atheroscler Rep 18(2):9. https://doi.org/10.1007/s11883-016-0559-4

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wirtz PH, von Kanel R (2017) Psychological stress, inflammation, and coronary heart disease. Curr Cardiol Rep 19(11):111. https://doi.org/10.1007/s11886-017-0919-x

    Article  PubMed  Google Scholar 

  9. De P, Aske JC, Dey N (2019) RAC1 takes the lead in solid tumors. Cells 8(5). https://doi.org/10.3390/cells8050382

  10. Harris KP, Tepass U (2010) Cdc42 and vesicle trafficking in polarized cells. Traffic 11(10):1272–1279. https://doi.org/10.1111/j.1600-0854.2010.01102.x

    Article  CAS  PubMed  Google Scholar 

  11. Ito TK, Yokoyama M, Yoshida Y et al (2014) A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis. PLoS One 9(7):e102186. https://doi.org/10.1371/journal.pone.0102186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li J, Liu Y, Jin Y et al (2017) Essential role of Cdc42 in cardiomyocyte proliferation and cell-cell adhesion during heart development. Dev Biol 421(2):271–283. https://doi.org/10.1016/j.ydbio.2016.12.012

    Article  CAS  PubMed  Google Scholar 

  13. AlBadri A, Wei J, Quesada O et al (2020) Coronary vascular function and cardiomyocyte injury: a report from the WISE-CVD. Arterioscler Thromb Vasc Biol 40(12):3015–3021. https://doi.org/10.1161/ATVBAHA.120.314260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tskvitaria-Fuller I, Seth A, Mistry N et al (2006) Specific patterns of Cdc42 activity are related to distinct elements of T cell polarization. J Immunol 177(3):1708–1720. https://doi.org/10.4049/jimmunol.177.3.1708

    Article  CAS  PubMed  Google Scholar 

  15. Guo F (2021) RhoA and Cdc42 in T cells: are they targetable for T cell-mediated inflammatory diseases? Precis Clin Med 4(1):56–61. https://doi.org/10.1093/pcmedi/pbaa039

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kalim KW, Yang JQ, Li Y et al (2018) Reciprocal regulation of glycolysis-driven Th17 pathogenicity and regulatory T cell stability by Cdc42. J Immunol 200(7):2313–2326. https://doi.org/10.4049/jimmunol.1601765

    Article  CAS  PubMed  Google Scholar 

  17. Herner M, Agasthi P (2021) Cardiac stress imaging, StatPearls, Treasure Island (FL)

  18. Gensini GG (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51(3):606. https://doi.org/10.1016/s0002-9149(83)80105-2

    Article  CAS  PubMed  Google Scholar 

  19. Sun N, Ye L, Chang T et al (2014) microRNA-195-Cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma. Int J Clin Exp Pathol 7(10):6871–6879

    PubMed  PubMed Central  Google Scholar 

  20. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  21. Mo XY, Li T, Hu ZP (2013) Decreased levels of cell-division cycle 42 (Cdc42) protein in peripheral lymphocytes from ischaemic stroke patients are associated with Golgi apparatus function. J Int Med Res 41(3):642–653. https://doi.org/10.1177/0300060513480093

    Article  CAS  PubMed  Google Scholar 

  22. Yang JQ, Kalim KW, Li Y et al (2019) Rational targeting Cdc42 restrains Th2 cell differentiation and prevents allergic airway inflammation. Clin Exp Allergy 49(1):92–107. https://doi.org/10.1111/cea.13293

    Article  CAS  PubMed  Google Scholar 

  23. Guo F, Zhang S, Tripathi P et al (2011) Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation. PLoS One 6(3):e18002. https://doi.org/10.1371/journal.pone.0018002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhong L, Simard MJ, Huot J (2018) Endothelial microRNAs regulating the NF-kappaB pathway and cell adhesion molecules during inflammation. FASEB J 32(8):4070–4084. https://doi.org/10.1096/fj.201701536R

    Article  CAS  PubMed  Google Scholar 

  25. Dong LM, Chen XW, He XX et al (2019) Cell division cycle protein 42 regulates the inflammatory response in mice bearing inflammatory bowel disease. Artif Cells Nanomed Biotechnol 47(1):1833–1838. https://doi.org/10.1080/21691401.2019.1596936

    Article  CAS  PubMed  Google Scholar 

  26. Harjunpaa H, Llort Asens M, Guenther C et al (2019) Cell adhesion molecules and their roles and regulation in the immune and tumor microenvironment. Front Immunol 10:1078. https://doi.org/10.3389/fimmu.2019.01078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bui TM, Wiesolek HL, Sumagin R (2020) ICAM-1: a master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol 108(3):787–799. https://doi.org/10.1002/JLB.2MR0220-549R

    Article  CAS  PubMed  Google Scholar 

  28. Price DT, Loscalzo J (1999) Cellular adhesion molecules and atherogenesis. Am J Med 107(1):85–97. https://doi.org/10.1016/s0002-9343(99)00153-9

    Article  CAS  PubMed  Google Scholar 

  29. Lv J, Zeng J, Guo F et al (2018) Endothelial Cdc42 deficiency impairs endothelial regeneration and vascular repair after inflammatory vascular injury. Respir Res 19(1):27. https://doi.org/10.1186/s12931-018-0729-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li Q, Zhang Z, Du R et al (2012) Association analysis between endothelial function related factors and coronary artery stenosis degree in coronary heart disease patients with type 2 diabetes mellitus. J Pediatr Endocrinol Metab 25(7–8):711–716. https://doi.org/10.1515/jpem-2012-0159

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Gang Tan.

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Zhou, M., Wu, J. & Tan, G. The relation of circulating cell division cycle 42 expression with Th1, Th2, and Th17 cells, adhesion molecules, and biochemical indexes in coronary heart disease patients. Ir J Med Sci 191, 2085–2090 (2022). https://doi.org/10.1007/s11845-021-02836-4

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