Int J Stomatol

Int J Stomatol ›› 2026, Vol. 53 ›› Issue (3): 370-380.doi: 10.7518/gjkq.2026018

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Advances in pyroptosis involved inthepathogenesis and progression of Porphyromonas gingivalis-accelerated atherosclerosis

Zixiang Wu(),Biyun Tan,Jinglei Zhan,Xia Li,Song Ge()   

  1. Dept. of Periodontology, Hospital of Stomatology, School of Stomatology, Zunyi Medical University, Zunyi 563000, China
  • Received:2025-03-26 Revised:2025-06-23 Online:2026-05-01 Published:2026-04-24
  • Contact: Song Ge E-mail:411004549@qq.com;gesong007b@163.com
  • Supported by:
    National Natural Science Foundation of China(82560193);Science and Technology Plan Projects of Zunyi Municipal Bureau of Industry and Science and Technology [No. (2024) 342]

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Abstract:

Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, induces local inflammation and has been recently confirmed to affect the vascular system via bloodstream dissemination or inflammatory mediators, closely associating it with cardiovascular diseases such as atherosclerosis. This article provides a systematic review of the mechanisms by which P. gingivalis promotes the initiation and progression of atherosclerosis through the pyroptosis pathway. It elucidates how P. gingivalis and its virulence factors activate pyroptosis signaling in vascular-related cells such as endothelial cells and smooth muscle cells, leading to the substantial production of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. This cascade exacerbates vascular inflammatory responses, promotes plaque formation, and induces instability. Innovatively centered on pyroptosis, which is a critical mechanism linking infection, inflammation, and programmed cell death, this review systematically consolidates evidence on how P. gingivalis regulates pyroptosis pathways to aggravate atherosclerosis. It also reveals novel pathways through which periodontal pathogens influence systemic diseases at the molecular and cellular levels. Furthermore, the article discusses the potential value of intervention strategies targeting key steps of pyroptosis in the treatment of atherosclerosis associated with periodontitis. This review integrates recent advances in microbe-host interactions and cell death to elucidate the comorbi-dity mechanism linking periodontitis and cardiovascular disease, while providing a theoretical basis for the development of targeted therapeutic strategies against pyroptosis.

Key words: Porphyromonas gingivalis, pyroptosis, periodontitis, atherosclerosis, cardiovascular disease

CLC Number: 

  • R780.2

TrendMD: 

Fig 1

Schematic illustration of the pathogenic mechanisms of P. gingivalis and its virulent factors in periodontitis"

Fig 2

Schematic diagram of pyroptosis activation"

Fig 3

Schematic diagram of the role of pyroptosis in P. gingivalis-accelerated As"

[1] Mekata M, Yoshida K, Takai A, et al. Porphyromo-nas gingivalis outer membrane vesicles increase vascular permeability by inducing stress fiber formation and degrading vascular endothelial-cadherin in endothelial cells[J]. FEBS J, 2025, 292: 1696-1709.
[2] Grenier D, Mayrand D. Functional characterization of extracellular vesicles produced by Bacteroides gingivalis [J]. Infect Immun, 1987, 55(1): 111-117.
[3] Ruan QJ, Guan P, Qi WJ, et al. Porphyromonas gingivalis regulates atherosclerosis through an immune pathway[J]. Front Immunol, 2023, 14: 1103592.
[4] Kannosh I, Staletovic D, Toljic B, et al. The pre-sence of periopathogenic bacteria in subgingival and atherosclerotic plaques-an age related compa-rative analysis[J]. J Infect Dev Ctries, 2018, 12(12): 1088-1095.
[5] Gusev E, Sarapultsev A. Atherosclerosis and inflammation: insights from the theory of general patholo-gical processes[J]. Int J Mol Sci, 2023, 24(9): 7910.
[6] Pedro-Botet J, Climent E, Benaiges D. Atherosclerosis and inflammation. New therapeutic approaches[J]. Med Clin, 2020, 155(6): 256-262.
[7] Fan JL, Watanabe T. Atherosclerosis: known and unknown[J]. Pathol Int, 2022, 72(3): 151-160.
[8] Xie SS, Deng Y, Guo SL, et al. Endothelial cell ferroptosis mediates monocrotaline-induced pulmonary hypertension in rats by modulating NLRP3 inflammasome activation[J]. Sci Rep, 2022, 12(1): 3056.
[9] Zhang XL, Wang ZY, Zheng YJ, et al. Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases[J]. Int J Mol Med, 2023, 51(4): 35.
[10] Naderi S, Merchant AT. The association between periodontitis and cardiovascular disease: an update[J]. Curr Atheroscler Rep, 2020, 22(10): 52.
[11] Li ZH, Huang QX, Wang ZR, et al. Effects of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans on modeling subgingival micro-biome and impairment of oral epithelial barrier[J]. J Infect Dis, 2024, 229(1): 262-272.
[12] 章可可, 孙妍, 潘乙怀. 牙龈卟啉单胞菌与非口腔疾病关系的研究进展[J]. 四川大学学报(医学版), 2023, 54(1): 20-26.
Zhang KK, Sun Y, Pan YH. Progress in the relationship between Porphyromonas gingivalis and non-oral diseases[J]. J Sichuan Univ (Med Sci Ed), 2023, 54(1): 20-26.
[13] Cortellini P, Cortellini S, Bonaccini D, et al. Modified minimally invasive surgical technique in human intrabony defects with or without regenerative materials-10-year follow-up of a randomized clinical trial: tooth retention, periodontitis recurrence, and costs[J]. J Clin Periodontol, 2022, 49(6): 528-536.
[14] 陈柔蓉. 抗牙龈卟啉单胞菌的脂质体——人参皂苷Rh2的制备及其在牙周炎治疗中的研究[D]. 武汉: 武汉大学, 2023.
Chen RR. Preparation of lipossome-ginsenoside Rh 2 against Porphyromonas gingivalis and its study in the treatment of periodontitis[D]. Wuhan: Wuhan University, 2023.
[15] 喻丽, 葛颂, 冯馨仪, 等. 牙龈卟啉单胞菌的研究进展[J]. 口腔疾病防治, 2016, 24(5): 314-317.
Yu L, Ge S, Feng XY, et al. Advances in Porphyromonas gingivalis [J]. Prev Treat Oral Dis, 2016, 24(5): 314-317.
[16] Olsen I, Yilmaz Ö. Modulation of inflammasome activity by Porphyromonas gingivalis in periodontitis and associated systemic diseases[J]. J Oral Micro-biol, 2016, 8: 30385.
[17] Guo XQ, Qiao GW, Wang JJ, et al. TIFA contributes to periodontitis in diabetic mice via activating the NF-κB signaling pathway[J]. Mol Med Rep, 2024, 29(2): 23.
[18] Chen WA, Dou Y, Fletcher HM, et al. Local and systemic effects of Porphyromonas gingivalis infection[J]. Microorganisms, 2023, 11(2): 470.
[19] Cheng X, Chi L, Lin TQ, et al. Exogenous monocy-te myeloid-derived suppressor cells ameliorate immune imbalance, neuroinflammation and cognitive impairment in 5xFAD mice infected with Porphyromonas gingivalis [J]. J Neuroinflammation, 2023, 20(1): 55.
[20] Okamura H, Hirota K, Yoshida K, et al. Outer membrane vesicles of Porphyromonas gingivalis: novel communication tool and strategy[J]. Jpn Dent Sci Rev, 2021, 57: 138-146.
[21] Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles[J]. Annu Rev Microbiol, 2010, 64: 163-184.
[22] Rao ZP, Zhu YT, Yang P, et al. Pyroptosis in inflammatory diseases and cancer[J]. Theranostics, 2022, 12(9): 4310-4329.
[23] Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases[J]. Trends Pharmacol Sci, 2022, 43(8): 653-668.
[24] Hsu SK, Li CY, Lin IL, et al. Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment[J]. Theranostics, 2021, 11(18): 8813-8835.
[25] Gao WT, Wang XY, Zhou Y, et al. Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy[J]. Signal Transduct Target Ther, 2022, 7(1): 196.
[26] Yu L, Huang K, Liao YX, et al. Targeting novel re-gulated cell death: Ferroptosis, pyroptosis and ne-croptosis in anti-PD-1/PD-L1 cancer immunotherapy[J]. Cell Prolif, 2024, 57(8): e13644.
[27] Li LP, Dickinson MS, Coers J, et al. Pyroptosis in defense against intracellular bacteria[J]. Semin Immunol, 2023, 69: 101805.
[28] Ding JJ, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family[J]. Nature, 2016, 535(7610): 111-116.
[29] Yu P, Zhang X, Liu N, et al. Pyroptosis: mechanisms and diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 128.
[30] Orning P, Weng D, Starheim K, et al. Pathogen bloc-kade of TAK1 triggers caspase-8-dependent cleava-ge of gasdermin D and cell death[J]. Science, 2018, 362(6418): 1064-1069.
[31] Wright SS, Kumari P, Fraile-Ágreda V, et al. Transplantation of gasdermin pores by extracellular ve-sicles propagates pyroptosis to bystander cells[J]. Cell, 2025, 188(2): 280-291.e17.
[32] Sanz M, Marco Del Castillo A, Jepsen S, et al. Pe-riodontitis and cardiovascular diseases: consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288.
[33] Wang XK, Xu Y, Yu CQ, et al. Periodontitis-related myocardial fibrosis by expansion of collagen-produ-cing SiglecF+ neutrophils[J]. Eur Heart J, 2025, 46(23): 2223-2238.
[34] Zhan PX, Feng ZY, Huang XQ, et al. Shared pyroptosis pathways and crosstalk genes underpin inflammatory links between periodontitis and atherosclerosis[J]. Immunobiology, 2025, 230(2): 152880.
[35] Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, et al. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis[J]. Pathog Dis, 2015, 73(4): ftv011.
[36] Yao F, Jin Z, Zheng ZH, et al. HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells[J]. Cell Death Discov, 2022, 8(1): 112.
[37] Mensah GA. Healthy endothelium: the scientific basis for cardiovascular health promotion and chronic disease prevention[J]. Vascul Pharmacol, 2007, 46(5): 310-314.
[38] Varghese JF, Patel R, Yadav UCS. Sterol regulatory element binding protein (SREBP)-1 mediates oxidized low-density lipoprotein (oxLDL) induced ma-crophage foam cell formation through NLRP3 inflammasome activation[J]. Cell Signal, 2019, 53: 316-326.
[39] He X, Fan XH, Bai B, et al. Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis[J]. Pharmacol Res, 2021, 165: 105447.
[40] Friedewald VE, Kornman KS, Beck JD, et al. The American journal of cardiology and journal of perio-dontology editors’ consensus: periodontitis and athe-rosclerotic cardiovascular disease[J]. Am J Cardiol, 2009, 104(1): 59-68.
[41] Li L, Michel R, Cohen J, et al. Intracellular survival and vascular cell-to-cell transmission of Porphyro-monas gingivalis [J]. BMC Microbiol, 2008, 8: 26.
[42] 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.
[43] Brown PM, Kennedy DJ, Morton RE, et al. CD36/SR-B2-TLR2 dependent pathways enhance Porphyromonas gingivalis mediated atherosclerosis in the Ldlr KO mouse model[J]. PLoS One, 2015, 10(5): e0125126.
[44] Liu J, Wang Y, Liao YY, et al. Circular RNA PPP-1CC promotes Porphyromonas gingivalis-lipopo-lysaccharide-induced pyroptosis of vascular smoo-th muscle cells by activating the HMGB1/TLR9/AIM2 pathway[J]. J Int Med Res, 2021, 49(3): 300060521996564.
[45] Park E, Na HS, Song YR, et al. Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection[J]. Infect Immun, 2014, 82(1): 112-123.
[46] Liu W, Liu J, Wang W, et al. NLRP6 induces pyroptosis by activation of caspase-1 in gingival fibroblasts[J]. J Dent Res, 2018, 97(12): 1391-1398.
[47] Fleetwood AJ, Lee MKS, Singleton W, et al. Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles[J]. Front Cell Infect Microbiol, 2017, 7: 351.
[48] Ding PH, Yang MX, Wang NN, et al. Porphyromo-nas gingivalis-induced NLRP3 inflammasome activation and its downstream interleukin-1β release depend on caspase-4[J]. Front Microbiol, 2020, 11: 1881.
[49] Fu SL, Qian YY, Dai AN, et al. Casp11 deficiency alters subgingival microbiota and attenuates perio-dontitis[J]. J Dent Res, 2024, 103(3): 298-307.
[50] Wu ZX, Ding Q, Yue MX, et al. Caspase-3/GSDME-mediated pyroptosis leads to osteogenic dysfunction of osteoblast-like cells[J]. Oral Dis, 2024, 30(3): 1392-1402.
[51] Gao XR, Li SH, Wang WX, et al. Caspase-3 and gasdermin E mediate macrophage pyroptosis in pe-riodontitis[J]. J Periodontal Res, 2024, 59(1): 140-150.
[52] Liu XH, Luo PY, Zhang WY, et al. Roles of pyroptosis in atherosclerosis pathogenesis[J]. Biomedecine Pharmacother, 2023, 166: 115369.
[53] Li M, Wang ZW, Fang LJ, et al. Programmed cell death in atherosclerosis and vascular calcification[J]. Cell Death Dis, 2022, 13(5): 467.
[54] Reina-Couto M, Pereira-Terra P, Quelhas-Santos J, et al. Inflammation in human heart failure: major mediators and therapeutic targets[J]. Front Physiol, 2021, 12: 746494.
[55] Molina A, Ambrosio N, Molina M, et al. Effect of periodontal therapy on endothelial function and serum biomarkers in patients with periodontitis and established cardiovascular disease: a pilot study[J]. Front Oral Health, 2025, 6: 1488941.
[56] 郑学彬, 龙淑会, 李富杰, 等. 老年慢性牙周炎合并冠心病患者龈沟液及血清中IL-1β、TNF-α、IL-18及IFN-γ的表达与临床意义[J]. 中国老年学杂志, 2020, 40(11): 2360-2363.
Zheng XB, Long SH, Li FJ, et al. Expression and clinical significance of IL-1β, TNF-α, IL-18 and IFN-γ in gingival crevicular fluid and serum of elderly patients with chronic periodontitis complica-ted with coronary heart disease [J]. Chin J Gerontol, 2020, 40 (11): 2360-2363.
[57] D’Aiuto F, Parkar M, Andreou G, et al. Periodontitis and atherogenesis: causal association or simple coincidence[J]. J Clin Periodontol, 2004, 31(5): 402-411.
[58] Li C, Yin WT, Yu N, et al. MiR-155 promotes macrophage pyroptosis induced by Porphyromonas gingivalis through regulating the NLRP3 inflammaso-me[J]. Oral Dis, 2019, 25(8): 2030-2039.
[59] Tang H, Ye Y, Li L, et al. A20 alleviated caspase-1-mediated pyroptosis and inflammation stimulated by Porphyromonas gingivalis lipopolysaccharide and nicotine through autophagy enhancement[J]. Hum Cell, 2022, 35(3): 803-816.
[60] Gu YY, Shen JY. Pentraxin-3 promotes LPS-indu-ced pyroptosis in human periodontal ligament stem cells[J]. Cells Tissues Organs, 2022, 211(5): 601-610.
[61] Wang LL, Pu WC, Wang C, et al. Microtubule affi-nity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in perio-dontitis[J]. J Oral Microbiol, 2022, 14(1): 2015130.
[62] Wu Q, Li Z, Zhang Y, et al. Cyclic di-AMP rescues Porphyromonas gingivalis-aggravated atherosclerosis[J]. J Dent Res, 2023, 102(7): 785-794.
[63] Li LL, Bian TY, Lyu JL, et al. Human β-defensin-3 alleviates the progression of atherosclerosis accele-rated by Porphyromonas gingivalis lipopolysaccharide[J]. Int Immunopharmacol, 2016, 38: 204-213.
[64] Xuan Y, Gao Y, Huang H, et al. Tanshinone ⅡA attenuates atherosclerosis in apolipoprotein E knockout mice infected with Porphyromonas gingivalis [J]. Inflammation, 2017, 40(5): 1631-1642.
[65] Pan SB, Lei L, Chen S, et al. Rosiglitazone impedes Porphyromonas gingivalis-accelerated atherosclerosis by downregulating the TLR/NF-κB signaling pa-thway in atherosclerotic mice[J]. Int Immunopharmacol, 2014, 23(2): 701-708.
[66] He WT, Wan HQ, Hu LC, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion[J]. Cell Res, 2015, 25(12): 1285-1298.
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