Research on Molecular Mechanism of Effect of Fusobacterium Nucleatum on Atherosclerosis

doi:10.13701/j.cnki.kqyxyj.2022.04.003

Abstract

Abstract: Atherosclerosis is an important morbidity and mortality cause of cardiovascular diseases such as coronary heart disease and stroke. It has been confirmed that periodontal disease is independently related to atherosclerosis. Fusobacterium nucleatum is a common pathogenic bacterium in the subgingival plaque of periodontitis. When periodontal tissue is in a state of inflammation, Fusobacterium nucleatum can enter the blood circulation through damaged capillaries, and then adhere to endothelial cells, destroying endothelial integrity and causing endothelial dysfunction. At the same time, Fusobacterium nucleatum and its heat shock protein can activate pro-inflammatory factors, enhance inflammatory response, lead to disorder of lipid metabolism, and eventually lead to the formation of atherosclerotic plaque. Therefore, this article reviews the possible molecular mechanisms of the interaction between Fusobacterium nucleatum and atherosclerosis.

Key words: atherosclerosis, Fusobacterium nucleatum, FadA, GroEL, inflammation, dyslipidemia

JIANG Duan, SHEN Daonan. Research on Molecular Mechanism of Effect of Fusobacterium Nucleatum on Atherosclerosis[J]. Journal of Oral Science Research, 2022, 38(4): 308-311.

References

[1] Schenkein HA, Papapanou PN, Genco R, et al. Mechanisms underlying the association between periodontitis and atherosclerotic disease[J]. Periodontol 2000, 2020, 83(1): 90-106.
[2] 左源,李维善.牙龈卟啉单胞菌脂多糖对人脐静脉内皮细胞表达小凹蛋白-1的影响[J].口腔医学研究,2020,36(1):75-78.
[3] Sanz M, Marco Del Castillo A, Jepsen S, et al. Periodontitis and cardiovascular diseases: Consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288.
[4] Liljestrand JM, Paju S, Pietiainen M, et al. Immunologic burden links periodontitis to acute coronary syndrome[J]. Atherosclerosis, 2018, 268: 177-184.
[5] Xie M, Tang Q, Nie J, et al. BMAL1-downregulation aggravates porphyromonas gingivalis-induced atherosclerosis by encouraging oxidative stress[J]. Circ Res, 2020, 126(6): e15-e29.
[6] Chukkapalli SS, Easwaran M, Rivera-Kweh MF, et al. Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice[J]. Pathog Dis, 2017, 75(1):ftx003.
[7] Deng ZL, Sztajer H, Jarek M, et al. Worlds apart-transcriptome profiles of key oral microbes in the periodontal pocket compared to single laboratory culture reflect synergistic interactions[J]. Front Microbiol, 2018, 9: 124.
[8] Han YW, Ikegami A, Rajanna C, et al. Identification and characterization of a novel adhesin unique to oral fusobacteria[J]. J Bacteriol, 2005, 187(15): 5330-5340.
[9] Temoin S, Wu KL, Wu V, et al. Signal peptide of FadA adhesin from Fusobacterium nucleatum plays a novel structural role by modulating the filament's length and width[J]. FEBS Lett, 2012, 586(1): 1-6.
[10] Fardini Y, Wang X, Temoin S, et al. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity[J]. Mol Microbiol, 2011, 82(6): 1468-1480.
[11] Leishman SJ, Ford PJ, Do HL, et al. Periodontal pathogen load and increased antibody response to heat shock protein 60 in patients with cardiovascular disease[J]. J Clin Periodontol, 2012, 39(10): 923-930.
[12] Duan Y, Tang H, Mitchell-Silbaugh K, et al. Heat shock protein 60 in cardiovascular physiology and diseases[J]. Front Mol Biosci, 2020, 7: 73.
[13] Lee HR, Jun HK, Kim HD, et al. Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human microvascular endothelial cells and ApoE(-/-) mice[J]. Mol Oral Microbiol, 2012, 27(2): 109-123.
[14] Grover SP, Mackman N. Tissue factor in atherosclerosis and atherothrombosis[J]. Atherosclerosis, 2020, 307: 80-86.
[15] Hao E, Pang G, Du Z, et al. Peach kernel oil downregulates expression of tissue factor and reduces atherosclerosis in ApoE knockout mice[J]. Int J Mol Sci, 2019, 20(2):405.
[16] Fong LY, Ng CT, Yong YK, et al. Asiatic acid stabilizes cytoskeletal proteins and prevents TNF-alpha-induced disorganization of cell-cell junctions in human aortic endothelial cells[J]. Vascul Pharmacol, 2019, 117: 15-26.
[17] Wang Q, Zhao L, Xu C, et al. Fusobacterium nucleatum stimulates monocyte adhesion to and transmigration through endothelial cells[J]. Arch Oral Biol, 2019, 100: 86-92.
[18] Mendes RT, Nguyen D, Stephens D, et al. Endothelial cell response to fusobacterium nucleatum[J]. Infect Immun, 2016, 84(7): 2141-2148.
[19] Mendes RT, Nguyen D, Stephens D, et al. Hypoxia-induced endothelial cell responses- possible roles during periodontal disease[J]. Clin Exp Dent Res, 2018, 4(6): 241-248.
[20] Velsko IM, Chukkapalli SS, Rivera-Kweh MF, et al. Fusobacterium nucleatum alters atherosclerosis risk factors and enhances inflammatory markers with an atheroprotective immune response in ApoE(null) mice[J]. PLoS One, 2015, 10(6): e0129795.
[21] Sack GH Jr. Serum amyloid A- a review[J]. Mol Med, 2018, 24(1): 46.
[22] Ljunggren S, Bengtsson T, Karlsson H, et al. Modified lipoproteins in periodontitis: a link to cardiovascular disease?[J]. Biosci Rep, 2019, 39(3):BSR20181665.
[23] Nepomuceno R, Pigossi SC, Finoti LS, et al. Serum lipid levels in patients with periodontal disease: A meta-analysis and meta-regression[J]. J Clin Periodontol, 2017, 44(12): 1192-1207.
[24] Bale BF, Doneen AL, Vigerust DJ. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis[J]. Postgrad Med J, 2017, 93(1098): 215-220.
[25] Babashamsi MM, Koukhaloo SZ, Halalkhor S, et al. ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity[J]. Diabetes Metab Syndr, 2019, 13(2): 1529-1534.
[26] Rosenson RS, Brewer HB Jr, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease[J]. Nat Rev Cardiol, 2016, 13(1): 48-60.
[27] Bobryshev YV, Ivanova EA, Chistiakov DA, et al. Macrophages and their role in atherosclerosis: pathophysiology and transcriptome analysis[J]. Biomed Res Int, 2016, 2016: 9582430.
[28] Kim DJ, Rho JH, Woo BH, et al. Periodontal pathogens modulate lipid flux via fatty acid binding protein 4[J]. J Dent Res, 2019, 98(13): 1511-1520.
[29] Badimon L, Peña E, Arderiu G, et al. C-reactive protein in atherothrombosis and angiogenesis[J]. Front Immunol, 2018, 9: 430.
[30] Tułowiecka N, Kotlęga D, Prowans P, et al. The role of resolvins: EPA and DHA derivatives can be useful in the prevention and treatment of ischemic stroke[J]. Int J Mol Sci, 2020, 21(20):7628.
[31] Ghousifam N, Mortazavian H, Bhowmick R, et al. A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration[J]. Int J Biol Macromol, 2017, 97: 141-147.
[32] Gao S, Xue X, Yin J, et al. Danlou tablet inhibits the inflammatory reaction of high-fat diet-induced atherosclerosis in ApoE knockout mice with myocardial ischemia via the NF-kappaB signaling pathway[J]. J Ethnopharmacol, 2020, 263: 113158.
[33] Priyamvara A, Dey AK, Bandyopadhyay D, et al. Periodontal inflammation and the risk of cardiovascular disease[J]. Curr Atheroscler Rep, 2020, 22(7): 28.