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Role of macrophage polarization in periodontitis promoting atherosclerosis

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Abstract

Periodontitis is a chronic inflammatory destructive disease occurring in periodontal supporting tissues. Atherosclerosis(AS) is one of the most common cardiovascular diseases. Periodontitis can promote the development and progression of AS. Macrophage polarization is closely related to the development and progression of the above two diseases, respectively. The purpose of this animal study was to evaluate the effect of periodontitis on aortic lesions in atherosclerotic mice and the role of macrophage polarization in this process. 45 ApoE-/-male mice were randomly divided into three groups: control (NC), atherosclerosis (AS), and atherosclerosis with periodontitis (AS + PD). Micro CT, serological testing and pathological testing(hematoxylin–eosin staining, oil red O staining and Masson staining) were used for Evaluate the modeling situation. Immunohistochemistry(IHC) and immunofluorescence(IF) were performed to evaluate macrophage content and macrophage polarization in plaques. Cytokines associated with macrophage polarization were analyzed using quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(Elisa). The expression of macrophages in plaques was sequentially elevated in the NC, AS, and AS + PD groups(P < 0.001). The expression of M1 and M1-related cytokines showed the same trend(P < 0.05). The expression of M2 and M2-related cytokines showed the opposite trend(P < 0.05). The rate of M1/M2 showed that AS + PD > AS > NC. Our preliminary data support that experimental periodontitis can increase the content of macrophage in aortic plaques to exacerbate AS. Meanwhile, experimental periodontitis can increase M1 macrophages, and decrease M2 macrophages, increasing M1/M2 in the plaque.

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References

  1. Zhang J, Xie M, Huang X, et al. The effects of porphyromonas gingivalis on atherosclerosis-related cells. Front Immunol. 2021;12: 766560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rocha VZ, Rached FH, Miname MH. Insights into the role of inflammation in the management of atherosclerosis. J Inflamm Res. 2023;16:2223–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hemmati M, Kashanipoor S, Mazaheri P, Alibabaei F, Babaeizad A, Asli S, et al. Importance of gut microbiota metabolites in the development of cardiovascular diseases (CVD). Life Sci. 2023;329: 121947.

    Article  CAS  PubMed  Google Scholar 

  4. Pereira LC, Nascimento JCR, Rêgo JMC, Canuto KM, Crespo-Lopez ME, Alvarez-Leite JI, et al. Apolipoprotein E, periodontal disease and the risk for atherosclerosis: a review. Arch Oral Biol. 2019;98:204–12.

    Article  CAS  PubMed  Google Scholar 

  5. Wu Q, Li Z, Zhang Y, Luo K, Xu X, Li J, Cyclic di-AMP, et al. Rescues porphyromonas gingivalis-aggravated atherosclerosis. J Dent Res. 2023. https://doi.org/10.1177/00220345231162344.

    Article  PubMed  Google Scholar 

  6. Fan T, Guo K, Cao F, Deng Z, Liu B, Shi M, et al. Study on the effect of periodontitis on renal tissue in atherosclerotic mice. J Periodontal Res. 2023;58:655–67.

    Article  PubMed  Google Scholar 

  7. Leira Y, Iglesias-Rey R, Gómez-Lado N, Aguiar P, Sobrino T, D’Aiuto F, et al. Periodontitis and vascular inflammatory biomarkers: an experimental in vivo study in rats. Odontology. 2020;108:202–12.

    Article  CAS  PubMed  Google Scholar 

  8. Wu Y, Wang Y, Du L, Wang K, Wang S, Li G. The link between different infection forms of Porphyromonas gingivalis and acute myocardial infarction: a cross-sectional study. BMC Oral Health. 2023;23:63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Olchanheski LRJ, Sordi R, Oliveira JG, Alves GF, Mendes RT, Santos FA, et al. The role of potassium channels in the endothelial dysfunction induced by periodontitis. J Appl Oral Sci Rev FOB. 2018;26: e20180048.

    CAS  Google Scholar 

  10. Gheorghita D, Eördegh G, Nagy F, Antal M. Periodontal disease, a risk factor for atherosclerotic cardiovascular disease. Orv Hetil. 2019;160:419–25.

    Article  PubMed  Google Scholar 

  11. Rapone B, Ferrara E, Qorri E, Quadri MFA, Dipalma G, Mancini A, et al. Intensive periodontal treatment does not affect the lipid profile and endothelial function of patients with type 2 diabetes: a randomized clinical trial. Biomedicines. 2022. https://doi.org/10.3390/biomedicines10102524.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Atri C, Guerfali FZ, Laouini D. Role of human macrophage polarization in inflammation during infectious diseases. Int J Mol Sci. 2018. https://doi.org/10.3390/ijms19061801.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wang Y, Wang Q, Xu D. New insights into macrophage subsets in atherosclerosis. J Mol Med (Berl). 2022;100:1239–51.

    Article  CAS  PubMed  Google Scholar 

  14. S Mummolo G, Botticelli V, Quinzi G, Giuca L, Mancini G, Marzo (2020) Implant-safe test in patients with peri-implantitis 100(147) 53

  15. Lira-Junior R, Holmström SB, Clark R, Zwicker S, Majster M, Johannsen G, et al. S100A12 Expression is modulated during monocyte differentiation and reflects periodontitis severity. Front Immunol. 2020;11:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Parisi L, Gini E, Baci D, Tremolati M, Fanuli M, Bassani B, et al. Macrophage polarization in chronic inflammatory diseases: killers or builders? J Immunol Res. 2018;2018:8917804.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yu T, Gao M, Yang P, Liu D, Wang D, Song F, et al. Insulin promotes macrophage phenotype transition through PI3K/Akt and PPAR-γ signaling during diabetic wound healing. J Cell Physiol. 2019;234:4217–31.

    Article  CAS  PubMed  Google Scholar 

  18. Sun X, Gao J, Meng X, Lu X, Zhang L, Chen R. Polarized macrophages in periodontitis: characteristics, function, and molecular signaling. Front Immunol. 2021;12: 763334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shao B, Han B, Zeng Y, Su D, Liu C. The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin. 2016;37:150–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wculek SK, Dunphy G, Heras-Murillo I, Mastrangelo A, Sancho D. Metabolism of tissue macrophages in homeostasis and pathology. Cell Mol Immunol. 2022;19:384–408.

    Article  CAS  PubMed  Google Scholar 

  21. Barrett TJ. Macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol. 2020;40:20–33.

    Article  CAS  PubMed  Google Scholar 

  22. Lin J, Huang D, Xu H, Zhan F, Tan X. Macrophages: a communication network linking porphyromonas gingivalis infection and associated systemic diseases. Front Immunol. 2022;13: 952040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wu Y, Xu W, Hou J, Liu Y, Li R, Liu J, et al. Porphyromonas gingivalis-induced MIF regulates intercellular adhesion molecule-1 expression in EA.hy926 cells and monocyte-endothelial cell adhesion through the receptors CD74 and CXCR4. Inflammation. 2019;42:874–83.

    Article  CAS  PubMed  Google Scholar 

  24. Liu F, Wang Y, Xu J, Liu F, Hu R, Deng H. Effects of porphyromonas gingivalis lipopolysaccharide on the expression of key genes involved in cholesterol metabolism in macrophages. Archiv Med Sci AMS. 2016;12:959–67.

    Article  CAS  Google Scholar 

  25. Zhou J, Liu L, Wu P, Zhao L, Wu Y. Fusobacterium nucleatum accelerates atherosclerosis via macrophage-driven aberrant proinflammatory response and lipid metabolism. Front Microbiol. 2022;13: 798685.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Alhassani AA, Hu FB, Li Y, Rosner BA, Willett WC, Joshipura KJ. The associations between major dietary patterns and risk of periodontitis. J Clin Periodontol. 2021;48:2–13.

    Article  PubMed  Google Scholar 

  27. Zhu X, Huang H, Zhao L. PAMPs and DAMPs as the Bridge between periodontitis and atherosclerosis: the potential therapeutic targets. Front Cell Dev Biol. 2022;10: 856118.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Suh JS, Kim S, Boström KI, Wang C, Kim RH, Park N. Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial-mesenchymal transition in mice. Int J Oral Sci. 2019;11:21.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Spiller KL, Nassiri S, Witherel CE, Anfang RR, Ng J, Nakazawa KR, et al. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials. 2015;37:194–207.

    Article  CAS  PubMed  Google Scholar 

  30. Gliozzi M, Scicchitano M, Bosco F, Musolino V, Carresi C, Scarano F, et al. Modulation of nitric oxide synthases by oxidized ldls: role in vascular inflammation and atherosclerosis development. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20133294.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mylonas KJ, Jenkins SJ, Castellan RFP, Ruckerl D, McGregor K, Phythian-Adams AT, et al. The adult murine heart has a sparse, phagocytically active macrophage population that expands through monocyte recruitment and adopts an “M2” phenotype in response to Th2 immunologic challenge. Immunobiology. 2015;220:924–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hu Z, Shi X, Yu B, Li N, Huang Y, He Y. Structural insights into the ph-dependent conformational change and collagen recognition of the human mannose receptor. Structure. 2018;26:60–71.

    Article  PubMed  Google Scholar 

  33. Paul S, Chhatar S, Mishra A, Lal G. Natural killer T cell activation increases iNOS(+)CD206(-) M1 macrophage and controls the growth of solid tumor. J Immunother Cancer. 2019;7:208.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ho TWW, Henry A, Lee WL. LDL transcytosis by the arterial endothelium-atherosclerosis by a thousand cuts? Curr Atheroscler Rep. 2023. https://doi.org/10.1007/s11883-023-01118-x.

    Article  PubMed  Google Scholar 

  35. Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol. 2021;18:58–68.

    Article  CAS  PubMed  Google Scholar 

  36. Pourcet B, Pineda-Torra I. Transcriptional regulation of macrophage arginase 1 expression and its role in atherosclerosis. Trends Cardiovasc Med. 2013;23:143–52.

    Article  CAS  PubMed  Google Scholar 

  37. Xu S, Zhang J, Liu J, Ye J, Xu Y, Wang Z, et al. The role of interleukin-10 family members in cardiovascular diseases. Int Immunopharmacol. 2021;94: 107475.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang Q, Huang F, Yao Y, Wang J, Wei J, Wu Q, et al. Interaction of transforming growth factor-β-Smads/microRNA-362-3p/CD82 mediated by M2 macrophages promotes the process of epithelial-mesenchymal transition in hepatocellular carcinoma cells. Cancer Sci. 2019;110:2507–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mainas G, Ide M, Rizzo M, Magan-Fernandez A, Mesa F, Nibali L. Managing the systemic impact of periodontitis. Medicina (Kaunas). 2022. https://doi.org/10.3390/medicina58050621.

    Article  PubMed  Google Scholar 

  40. Li H, Cao Z, Wang L, Liu C, Lin H, Tang Y, et al. Macrophage subsets and death are responsible for atherosclerotic plaque formation. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.843712.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by grants from the Beijing-Tianjin-Hebei Region's Medical and Health Coordinated Development and Public HospitalNoReform Capacity Building of China (2019061636).

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Beijing-Tianjin-Hebei Region’s Medical and Health Coordinated Development and Public HospitalNoReform Capacity Building of China,2019061636,zhe ma

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Shi, M., Guo, K., Liu, Y. et al. Role of macrophage polarization in periodontitis promoting atherosclerosis. Odontology (2024). https://doi.org/10.1007/s10266-024-00935-z

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