Int J Stomatol

Int J Stomatol ›› 2025, Vol. 52 ›› Issue (3): 308-316.doi: 10.7518/gjkq.2025055

• Periodontitis • Previous Articles     Next Articles

Research progress into the effects of Porphyromonas gingivalis on regulatory cell death and phenotypic switching of vascular smooth muscle cells

Mengyao Bie(),Jieyu Zhou,Yafei Wu,Lei Zhao()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Dept. of Periodontology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2024-03-19 Revised:2024-05-05 Online:2025-05-01 Published:2025-04-30
  • Contact: Lei Zhao E-mail:15090378950@163.com;jollyzldoc@163.com
  • Supported by:
    National Natural Science Foundation of China(81970944);National Natural Science Foundation of China Youth Fund(82301089);Research and Develop Program, West China Hospital of Stomatology, Sichuan University(RD-02-202407)

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Abstract:

Periodontitis is a chronic inflammatory disease caused by bacterial infection. Epidemiological studies and in vivo/in vitro research have consistently demonstrated a strong association between periodontitis and an increased risk of cardiovascular diseases. Vascular smooth muscle cells (VSMCs) participate in the pathogenesis of atherosclerosis, aortic aneurysms, and vascular calcification via regulated cell death mechanisms (including autophagy, apoptosis, and pyroptosis) and phenotypic switching. Porphyromonas gingivalis, a critical periodontal pathogen, alters VSMC biological beha-vior, not only invading VSMCs to influence their regulated cell death process but also promoting phenotypic switching characterized by proliferation, migration, and calcification. These mechanisms play pivotal roles in cardiovascular disease development. This review aims to synthesize recent research advances and elucidate the connections between periodontitis and VSMC-regulated cell death/phenotypic switching. Novel insights into improved prevention and treatment strategies for periodontitis and cardiovascular diseases are provided.

Key words: Porphyromonas gingivalis, vascular smooth muscle cell, cardiovascular diseases, phenotypic switching, periodontitis

CLC Number: 

  • R780.2

TrendMD: 
1 Louhelainen AM, Aho J, Tuomisto S, et al. Oral bacterial DNA findings in pericardial fluid[J]. J Oral Microbiol, 2014, 6: 25835.
2 Moreno S, Parra B, Botero JE, et al. Periodontal microbiota and microorganisms isolated from heart valves in patients undergoing valve replacement surgery in a clinic in Cali, Colombia[J]. Biomedica, 2017, 37(4): 516-525.
3 Kozarov E, Sweier D, Shelburne C, et al. Detection of bacterial DNA in atheromatous plaques by quantitative PCR[J]. Microbes Infect, 2006, 8(3): 687-693.
4 Ziebolz D, Jahn C, Pegel J, et al. Periodontal bacteria DNA findings in human cardiac tissue-is there a link of periodontitis to heart valve disease[J]. Int J Cardiol, 2018, 251: 74-79.
5 Sanz M, Marco Del Castillo A, Jepsen S, et al. Perio-dontitis and cardiovascular diseases: consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288.
6 Olsen I, Singhrao SK, Potempa J. Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease[J]. J Oral Microbiol, 2018, 10(1): 1487742.
7 Schenkein HA, Papapanou PN, Genco R, et al. Mechanisms underlying the association between periodontitis and atherosclerotic disease[J]. Perio- dontol 2000, 2020, 83(1): 90-106.
8 Imbronito AV, Okuda OS, Maria de Freitas N, et al. Detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis[J]. J Periodontol, 2008, 79(12): 2313-2321.
9 Figuero E, Sánchez-Beltrán M, Cuesta-Frechoso S, et al. Detection of periodontal bacteria in atheromatous plaque by nested polymerase chain reaction[J]. J Periodontol, 2011, 82(10): 1469-1477.
10 Xie MR, Tang QM, Nie JM, et al. BMAL1-downregulation aggravates Porphyromonas gingivalis-induced atherosclerosis by encouraging oxidative stress[J]. Circ Res, 2020, 126(6): e15-e29.
11 Xie MR, Tang QM, Yu SL, et al. Porphyromonas gingivalis disrupts vascular endothelial homeostasis in a TLR-NF-κB axis dependent manner[J]. Int J Oral Sci, 2020, 12(1): 28.
12 Park MH, Jeong SY, Na HS, et al. Porphyromonas gingivalis induces autophagy in THP-1-derived ma-crophages[J]. Mol Oral Microbiol, 2017, 32(1): 48-59.
13 Zhang JQ, Xie MR, Huang XF, et al. The effects of Porphyromonas gingivalis on atherosclerosis-rela-ted cells[J]. Front Immunol, 2021, 12: 766560.
14 Furmanik M, Chatrou M, van Gorp R, et al. Reactive oxygen-forming Nox5 links vascular smooth muscle cell phenotypic switching and extracellular vesicle-mediated vascular calcification[J]. Circ Res, 2020, 127(7): 911-927.
15 Wan XQ, Zhang H, Tian JF, et al. The chains of ferroptosis interact in the whole progression of atherosclerosis[J]. J Inflamm Res, 2023, 16: 4575-4592.
16 Dorn BR, Dunn WA Jr, Progulske-Fox A. Invasion of human coronary artery cells by periodontal pathogens[J]. Infect Immun, 1999, 67(11): 5792-5798.
17 Kozarov EV, Dorn BR, Shelburne CE, et al. Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis [J]. Arterioscler Thromb Vasc Biol, 2005, 25(3): e17-e18.
18 Zhang BX, Sirsjö A, Khalaf H, et al. Transcriptional profiling of human smooth muscle cells infected with gingipain and fimbriae mutants of Porphyromonas gingivalis [J]. Sci Rep, 2016, 6: 21911.
19 Roth GA, Aumayr K, Giacona MB, et al. Porphyromonas gingivalis infection and prothrombotic effects in human aortic smooth muscle cells[J]. Thromb Res, 2009, 123(5): 780-784.
20 Kozarov E. Bacterial invasion of vascular cell types: vascular infectology and atherogenesis[J]. Future Cardiol, 2012, 8(1): 123-138.
21 Olsen I, Progulske-Fox A. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue[J]. J Oral Microbiol, 2015, 7: 28788.
22 Osonoi Y, Mita T, Azuma K, et al. Defective auto-phagy in vascular smooth muscle cells enhances cell death and atherosclerosis[J]. Autophagy, 2018, 14(11): 1991-2006.
23 Clarke MCH, Littlewood TD, Figg N, et al. Chronic apoptosis of vascular smooth muscle cells accele-rates atherosclerosis and promotes calcification and medial degeneration[J]. Circ Res, 2008, 102(12): 1529-1538.
24 Xie HY, Qin ZY, Ling ZJ, et al. Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis[J]. Int J Oral Sci, 2023, 15(1): 26.
25 Park HJ, Kim Y, Kim MK, et al. Infection of Porphyromonas gingivalis increases phosphate-induced calcification of vascular smooth muscle cells[J]. Cells, 2020, 9(12): 2694.
26 Gupta M, Chaturvedi R, Jain A. Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease[J]. Cytokine, 2013, 61(3): 892-897.
27 Damgaard C, Kantarci A, Holmstrup P, et al. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1[J]. J Periodontal Res, 2017, 52(2): 246-254.
28 Bodet C, Chandad F, Grenier D. Porphyromonas gingivalis-induced inflammatory mediator profile in an ex vivo human whole blood model[J]. Clin Exp Immunol, 2006, 143(1): 50-57.
29 Saitoh T, Fujita N, Jang MH, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production[J]. Nature, 2008, 456(7219): 264-268.
30 Liu J, Wang Y, Liao YY, et al. Circular RNA PPP1CC promotes Porphyromonas gingivalis-lipopolysaccharide-induced pyroptosis of vascular s-mooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway[J]. J Int Med Res, 2021, 49(3): 300060521996564.
31 Kolb S, Vranckx R, Huisse MG, et al. The phosphatidylserine receptor mediates phagocytosis by vascular smooth muscle cells[J]. J Pathol, 2007, 212(3): 249-259.
32 Sorokin V, Vickneson K, Kofidis T, et al. Role of vascular smooth muscle cell plasticity and interactions in vessel wall inflammation[J]. Front Immunol, 2020, 11: 599415.
33 Mnjoyan ZH, Doan D, Brandon JL, et al. The critical role of the intrinsic VSMC proliferation and death programs in injury-induced neointimal hyperplasia[J]. Am J Physiol Heart Circ Physiol, 2008, 294(5): H2276-H2284.
34 Allahverdian S, Chaabane C, Boukais K, et al. Smooth muscle cell fate and plasticity in atherosclerosis[J]. Cardiovasc Res, 2018, 114(4): 540-550.
35 Lee SJ, Lee IK, Jeon JH. Vascular calcification-new insights into its mechanism[J]. Int J Mol Sci, 2020, 21(8): 2685.
36 Leopold JA. Vascular calcification: mechanisms of vascular smooth muscle cell calcification[J]. Trends Cardiovasc Med, 2015, 25(4): 267-274.
37 Inaba H, Hokamura K, Nakano K, et al. Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen[J]. FEBS Lett, 2009, 583(1): 128-134.
38 Li WF, Zhi WB, Zhao JM, et al. Cinnamaldehyde protects VSMCs against ox-LDL-induced proliferation and migration through S arrest and inhibition of p38, JNK/MAPKs and NF‑κB[J]. Vascul Pharmacol, 2018, 108: 57-66.
39 Yu N, Shen AL, Chu JF, et al. Qingda granule inhi-bits angiotensin Ⅱ induced VSMCs proliferation through MAPK and PI3K/AKT pathways[J]. J Ethnopharmacol, 2020, 258: 112767.
40 Inaba H, Tagashira M, Kanda T, et al. Proliferation of smooth muscle cells stimulated by Porphyromo-nas gingivalis is inhibited by apple polyphenol[J]. J Periodontol, 2011, 82(11): 1616-1622.
41 Cao C, Luo X, Ji XW, et al. Osteopontin regulates the proliferation of rat aortic smooth muscle cells in response to gingipains treatment[J]. Mol Cell Probes, 2017, 33: 51-56.
42 Cao C, Ji XW, Luo X, et al. Gingipains from Porphyromonas gingivalis promote the transformation and proliferation of vascular smooth muscle cell phenotypes[J]. Int J Clin Exp Med, 2015, 8(10): 18327-18334.
43 Khalaf H, Lönn J, Bengtsson T. Cytokines and chemokines are differentially expressed in patients with periodontitis: possible role for TGF-β1 as a marker for disease progression[J]. Cytokine, 2014, 67(1): 29-35.
44 Deng HB, Jiang CQ, Tomlinson B, et al. A polymorphism in transforming growth factor-β1 is associa-ted with carotid plaques and increased carotid intima-media thickness in older Chinese men: the Guangzhou biobank cohort study-cardiovascular disease subcohort[J]. Atherosclerosis, 2011, 214(2): 391-396.
45 Suwanabol PA, Seedial SM, Shi XD, et al. Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinases pathways[J]. J Vasc Surg, 2012, 56(2): 446-454.
46 Wada K, Kamisaki Y. Roles of oral bacteria in cardiovascular diseases: from molecular mechanisms to clinical cases: involvement of Porphyromonas gingivalis in the development of human aortic aneurysm[J]. J Pharmacol Sci, 2010, 113(2): 115-119.
47 Hokamura K, Umemura K. Roles of oral bacteria in cardiovascular diseases: from molecular mechanisms to clinical cases: Porphyromonas gingivalis is the important role of intimal hyperplasia in the aorta[J]. J Pharmacol Sci, 2010, 113(2): 110-114.
48 Miyabe M, Nakamura N, Saiki T, et al. Porphyromonas gingivalis lipopolysaccharides promote prolife-ration and migration of human vascular smooth muscle cells through the MAPK/TLR4 pathway[J]. Int J Mol Sci, 2022, 24(1): 125.
49 李霞, 胡琳琳, 何权敏, 等. 牙龈卟啉单胞菌脂多糖对共培养体系中人脐动脉平滑肌细胞增殖及迁移能力的影响[J]. 中华口腔医学杂志, 2021, 56(6): 549-556.
Li X, Hu LL, He QM, et al. Effects of Porphyromonas gingivalis lipopolysaccharide on the proliferation and migration of human umbilical artery smooth muscle cells under co-culture conditions[J]. Chin J Stomatol, 2021, 56(6): 549-556.
50 赵瑜敏, 张明珠, 税艳青, 等. 牙龈卟啉单胞菌对兔血管平滑肌细胞增殖和迁移的影响[J]. 昆明医科大学学报, 2013, 34(3): 22-25.
Zhao YM, Zhang MZ, Shui YQ, et al. Effects of proliferation and migration on the vascular smooth muscle cells of rabbit stimulated by Porphyromonas gingivalis [J]. J Kunming Med Univ, 2013, 34(3): 22-25.
51 Zhang F, Ren XS, Zhao MX, et al. Angiotensin-(1-7) abrogates angiotensin Ⅱ-induced proliferation, migration and inflammation in VSMCs through inac-tivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways[J]. Sci Rep, 2016, 6: 34621.
52 Ben PL, Hu MN, Wu HZ, et al. L-theanine down-regulates the JAK/STAT3 pathway to attenuate the proliferation and migration of vascular smooth muscle cells induced by angiotensin Ⅱ[J]. Biol Pharm Bull, 2018, 41(11): 1678-1684.
53 Strela FB, Brun BF, Berger RCM, et al. Lipopolysaccharide exposure modulates the contractile and migratory phenotypes of vascular smooth muscle cells[J]. Life Sci, 2020, 241: 117098.
54 Kim Y, Kim SJ, Kim MK, et al. Porphyromonas gingivalis lipopolysaccharide regulates migration of vascular smooth muscle cells[J]. Int J Oral Biol, 2016, 41(4): 217-223.
55 Isola G, Polizzi A, Ronsivalle V, et al. Impact of matrix metalloproteinase-9 during periodontitis and cardiovascular diseases[J]. Molecules, 2021, 26(6): 1777.
56 Durham AL, Speer MY, Scatena M, et al. Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness[J]. Cardiovasc Res, 2018, 114(4): 590-600.
57 Liu GR, Deng J, Zhang Q, et al. Porphyromonas gingivalis lipopolysaccharide stimulation of vascular smooth muscle cells activates proliferation and calcification[J]. J Periodontol, 2016, 87(7): 828-836.
58 Yang WW, Guo B, Jia WY, et al. Porphyromonas gingivalis-derived outer membrane vesicles promote calcification of vascular smooth muscle cells through ERK1/2-RUNX2[J]. FEBS Open Bio, 2016, 6(12): 1310-1319.
59 Li J, Deng J, Shang SX, et al. Effect of Porphyromonas gingivalis lipopolysaccharide on calcification of human umbilical artery smooth muscle cells co-cultured with human periodontal ligament cells[J]. Exp Ther Med, 2021, 21(6): 655.
60 Chen TC, Lin CT, Chien SJ, et al. Regulation of calcification in human aortic smooth muscle cells infected with high-glucose-treated Porphyromonas gingivalis [J]. J Cell Physiol, 2018, 233(6): 4759-4769.
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