国际口腔医学杂志

国际口腔医学杂志 ›› 2025, Vol. 52 ›› Issue (3): 308-316.doi: 10.7518/gjkq.2025055

• 牙周专栏 • 上一篇    下一篇

牙龈卟啉单胞菌影响血管平滑肌细胞调节性细胞死亡及表型转换的研究进展

别梦瑶(),周婕妤,吴亚菲,赵蕾()   

  1. 口腔疾病防治全国重点实验室 国家口腔医学中心 国家口腔疾病临床医学研究中心四川大学华西口腔医院牙周病科 成都 610041
  • 收稿日期:2024-03-19 修回日期:2024-05-05 出版日期:2025-05-01 发布日期:2025-04-30
  • 通讯作者: 赵蕾
  • 作者简介:别梦瑶，硕士，Email：15090378950@163.com
  • 基金资助:
    国家自然科学基金(81970944);国家自然科学基金青年科学基金(82301089);四川大学华西口腔医院探索与研发项目(RD-02-202407)

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
  • 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)

RichHTML

7

PDF (PC)

78

摘要：

牙周炎是由细菌感染引起的慢性炎症性疾病。流行病学和体内外研究均表明牙周炎与心血管疾病风险增加密切相关。血管平滑肌细胞通过自噬、凋亡、焦亡等调节性细胞死亡和表型转换参与动脉粥样硬化、主动脉瘤、血管钙化等心血管疾病的发生发展。牙龈卟啉单胞菌是最重要的牙周致病菌之一，已被证明可以改变血管平滑肌细胞的生物学行为，不仅能侵入血管平滑肌细胞影响其调节性细胞死亡的过程，还能促进其增殖、迁移、钙化等表型转换，在心血管疾病的发生发展中发挥重要作用。本文旨在梳理相关研究进展，以期揭示牙周炎和血管平滑肌细胞调节性细胞死亡及其表型转换之间的联系，为更好地防治牙周炎和心血管疾病提供思路。

关键词: 牙龈卟啉单胞菌, 血管平滑肌细胞, 心血管疾病, 表型转换, 牙周炎

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

中图分类号: 

  • R780.2
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.
[1] 李天元,朱彤欣,柳庆,董迎春,陈斌. 间充质干细胞用于牙周再生临床疗效的系统评价与Meta分析[J]. 国际口腔医学杂志, 2025, 52(3): 296-307.
[2] 范兴丽,潘乐,赵家园,项秋猛,陈启林. 竞争性内源性RNA在牙周炎中的作用及机制的研究进展[J]. 国际口腔医学杂志, 2025, 52(3): 317-322.
[3] 赵美林,赵依琼,黄姣. Ⅲ期C级牙周炎正畸患者上前牙龈乳头缺陷伴牙龈退缩1例[J]. 国际口腔医学杂志, 2025, 52(3): 333-340.
[4] 李晶,康健. 牙周微创手术中再生材料选择及疗效的研究进展[J]. 国际口腔医学杂志, 2025, 52(2): 161-168.
[5] 张潇月,陈舒泽,周婕妤,程磊,赵蕾. 具核梭杆菌经铁死亡途径破坏体外肠道上皮屏障模型的研究[J]. 国际口腔医学杂志, 2025, 52(2): 183-194.
[6] 钟良军. 数字化技术在重度牙周炎治疗中的应用[J]. 国际口腔医学杂志, 2025, 52(1): 1-10.
[7] 程守正,李太文,赵蕾. 血清淀粉样蛋白A与牙周炎相关性的研究进展[J]. 国际口腔医学杂志, 2025, 52(1): 117-122.
[8] 陈梦洁,徐文华,刘青青,康毓聃,刘蓉,朱丽雷. 全身免疫炎症指数与牙周炎患者分级诊断的相关性研究[J]. 国际口腔医学杂志, 2024, 51(6): 706-712.
[9] 陈蕊,范桢,郝春波. 黑色素瘤缺乏因子2炎症小体在牙周炎及糖尿病中的研究进展[J]. 国际口腔医学杂志, 2024, 51(6): 763-771.
[10] 张睿,郝婷,吕闻,任双双,刘玉,吴文蕾,孙卫斌. 载黄连素的同轴静电纺丝膜对牙周致病菌及生物膜的抑菌性研究[J]. 国际口腔医学杂志, 2024, 51(5): 596-607.
[11] 毛鸿晨,王铮,杨德琴. 牙龈卟啉单胞菌外膜囊泡在口腔疾病中的作用及其机制的研究进展[J]. 国际口腔医学杂志, 2024, 51(5): 608-615.
[12] 漆美瑶,祁星颖,周欣奕,谭震,袁泉. 大麻二酚联合米诺环素对牙周炎治疗作用的实验研究[J]. 国际口腔医学杂志, 2024, 51(4): 392-400.
[13] 陈梦洁, 刘小乐, 朱丽雷. 牙周炎患者牙周支持治疗对血细胞指标影响的回顾性研究[J]. 国际口腔医学杂志, 2024, 51(4): 401-405.
[14] 马玉, 左玉, 刘建华. 抗菌光动力疗法与全身抗菌药物辅助治疗牙周炎疗效比较的Meta分析[J]. 国际口腔医学杂志, 2024, 51(4): 406-415.
[15] 刘诗礼, 赵蕾. 牙周炎与心力衰竭相关性的研究进展[J]. 国际口腔医学杂志, 2024, 51(4): 425-432.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!