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Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis

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Abstract

Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE−/− mice with P. gingivalis infection. Eight-week-old ApoE−/− mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg−1 day−1). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects.

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Abbreviations

TSA:

Tanshinone IIA

P. gingivalis :

Porphyromonas gingivalis

ApoE−/− mice:

Apolipoprotein E knockout mice

AS:

Atherosclerosis

PBS:

Phosphate-buffered saline

GAPDH:

Glyceraldehydes 3-phosphate dehydrogenase

bFGF:

Basic fibroblast growth factor

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

IFN-γ:

Interferon-γ

VEGF:

Vascular endothelial growth factor

G-CSF:

Granulocyte-colony stimulating factor

MCP-1:

Monocyte chemoattractant protein-1

MIP-3α:

Macrophage inflammatory protein-3α

CRP:

C-reactive protein

IL-6:

Interleukin-6

IL-12:

Interleukin-12

ox-LDL:

Oxidized low-density lipoprotein

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

VLDL:

Very low-density lipoprotein

MMP-2:

Matrix metallopeptidase-2

MMP-9:

Matrix metallopeptidase-9

LOX-1:

Lectin-like ox-LDL receptor-1

COX-2:

Cyclooxygenase-2

FASN:

Fatty acid synthase

HMG-COA:

3-hydroxy-3-methylglutaryl coenzyme A

MI:

Myocardial infarction

ICAM-1:

Intercellular cell adhesion molecule-1

HUVECs:

Human umbilical vein endothelial cells

LPS:

Lipopolysaccharide

References

  1. Libby, P., P.M. Ridker, and G.K. Hansson. 2011. Progress and challenges in translating the biology of atherosclerosis. Nature 473 (7347): 317–325. doi:10.1038/nature10146.

    Article  CAS  PubMed  Google Scholar 

  2. Beck, J., R. Garcia, G. Heiss, P.S. Vokonas, and S. Offenbacher. 1996. Periodontal disease and cardiovascular disease. Journal of Periodontology 67 (10 Suppl): 1123–1137. doi:10.1902/jop.1996.67.10s.1123.

    Article  CAS  PubMed  Google Scholar 

  3. Grossi, S.G., and R.J. Genco. 1998. Periodontal disease and diabetes mellitus: A two-way relationship. Annals of Periodontology 3 (1): 51–61. doi:10.1902/annals.1998.3.1.51.

    Article  CAS  PubMed  Google Scholar 

  4. Straka, M., M. Straka-Trapezanlidis, J. Deglovic, and I. Varga. 2015. Periodontitis and osteoporosis. Neuro Endocrinology Letters 36 (5): 401–406.

    PubMed  Google Scholar 

  5. Bahekar, A.A., S. Singh, S. Saha, J. Molnar, and R. Arora. 2007. The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: A meta-analysis. American Heart Journal 154 (5): 830–837. doi:10.1016/j.ahj.2007.06.037.

    Article  PubMed  Google Scholar 

  6. Cai, Y., T. Kurita-Ochiai, T. Hashizume, and M. Yamamoto. 2013. Green tea epigallocatechin-3-gallate attenuates Porphyromonas gingivalis-induced atherosclerosis. Pathogens and disease 67 (1): 76–83. doi:10.1111/2049-632X.12001.

    Article  CAS  PubMed  Google Scholar 

  7. Champaiboon, C., M. Poolgesorn, W. Wisitrasameewong, N. Sa-Ard-Iam, P. Rerkyen, and R. Mahanonda. 2014. Differential inflammasome activation by Porphyromonas gingivalis and cholesterol crystals in human macrophages and coronary artery endothelial cells. Atherosclerosis 235 (1): 38–44. doi:10.1016/j.atherosclerosis.2014.04.007.

    Article  CAS  PubMed  Google Scholar 

  8. Chukkapalli, S.S., I.M. Velsko, M.F. Rivera-Kweh, D. Zheng, A.R. Lucas, and L. Kesavalu. 2015. Polymicrobial oral infection with four periodontal bacteria orchestrates a distinct inflammatory response and atherosclerosis in ApoE null mice. PloS One 10 (11): e0143291. doi:10.1371/journal.pone.0143291.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lin, G., S. Chen, L. Lei, X. You, M. Huang, L. Luo, Y. Li, X. Zhao, and F. Yan. 2015. Effects of intravenous injection of Porphyromonas gingivalis on rabbit inflammatory immune response and atherosclerosis. Mediators of Inflammation 2015: 364391. doi:10.1155/2015/364391.

    PubMed  PubMed Central  Google Scholar 

  10. Pan, S., L. Lei, S. Chen, H. Li, and F. Yan. 2014. Rosiglitazone impedes Porphyromonas gingivalis-accelerated atherosclerosis by downregulating the TLR/NF-kappaB signaling pathway in atherosclerotic mice. International Immunopharmacology 23 (2): 701–708. doi:10.1016/j.intimp.2014.10.026.

    Article  CAS  PubMed  Google Scholar 

  11. Deshpande, R.G., M.B. Khan, and C.A. Genco. 1998. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infection and Immunity 66 (11): 5337–5343.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Roth, G.A., K. Aumayr, M.B. Giacona, P.N. Papapanou, A.M. Schmidt, and E. Lalla. 2009. Porphyromonas gingivalis infection and prothrombotic effects in human aortic smooth muscle cells. Thrombosis Research 123 (5): 780–784. doi:10.1016/j.thromres.2008.07.008.

    Article  CAS  PubMed  Google Scholar 

  13. Libby, P., P.M. Ridker, and A. Maseri. 2002. Inflammation and atherosclerosis. Circulation 105 (9): 1135–1143.

    Article  CAS  PubMed  Google Scholar 

  14. Cheng, T.O. 2006. Danshen: A popular Chinese cardiac herbal drug. Journal of the American College of Cardiology 47 (7): 1498; author reply 1499–1500. doi:10.1016/j.jacc.2006.01.001.

    Article  PubMed  Google Scholar 

  15. Tang, F., X. Wu, T. Wang, P. Wang, R. Li, H. Zhang, J. Gao, S. Chen, L. Bao, H. Huang, and P. Liu. 2007. Tanshinone II A attenuates atherosclerotic calcification in rat model by inhibition of oxidative stress. Vascular Pharmacology 46 (6): 427–438. doi:10.1016/j.vph.2007.01.001.

    Article  CAS  PubMed  Google Scholar 

  16. Chen, Z., and H. Xu. 2014. Anti-inflammatory and immunomodulatory mechanism of Tanshinone IIA for atherosclerosis. Evidence-based complementary and alternative medicine : eCAM 2014: 267976. doi:10.1155/2014/267976.

    Google Scholar 

  17. Gong, Z., C. Huang, X. Sheng, Y. Zhang, Q. Li, M.W. Wang, L. Peng, and Y.Q. Zang. 2009. The role of Tanshinone IIA in the treatment of obesity through peroxisome proliferator-activated receptor gamma antagonism. Endocrinology 150 (1): 104–113. doi:10.1210/en.2008-0322.

    Article  CAS  PubMed  Google Scholar 

  18. Gao, S., Z. Liu, H. Li, P.J. Little, P. Liu, and S. Xu. 2012. Cardiovascular actions and therapeutic potential of tanshinone IIA. Atherosclerosis 220 (1): 3–10. doi:10.1016/j.atherosclerosis.2011.06.041.

    Article  CAS  PubMed  Google Scholar 

  19. Hayashi, C., J. Viereck, N. Hua, A. Phinikaridou, A.G. Madrigal, F.C. Gibson 3rd, J.A. Hamilton, and C.A. Genco. 2011. Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice. Atherosclerosis 215 (1): 52–59. doi:10.1016/j.atherosclerosis.2010.12.009.

    Article  CAS  PubMed  Google Scholar 

  20. Tang, F.T., Y. Cao, T.Q. Wang, L.J. Wang, J. Guo, X.S. Zhou, S.W. Xu, W.H. Liu, P.Q. Liu, and H.Q. Huang. 2011. Tanshinone IIA attenuates atherosclerosis in ApoE(−/−) mice through down-regulation of scavenger receptor expression. European Journal of Pharmacology 650 (1): 275–284. doi:10.1016/j.ejphar.2010.07.038.

    Article  CAS  PubMed  Google Scholar 

  21. Paigen, B., A. Morrow, P.A. Holmes, D. Mitchell, and R.A. Williams. 1987. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68 (3): 231–240.

    Article  CAS  PubMed  Google Scholar 

  22. Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25 (4): 402–408. doi:10.1006/meth.2001.1262.

    Article  CAS  PubMed  Google Scholar 

  23. Cutler, C.W., J.R. Kalmar, and C.A. Genco. 1995. Pathogenic strategies of the oral anaerobe, Porphyromonas gingivalis. Trends in Microbiology 3 (2): 45–51.

    Article  CAS  PubMed  Google Scholar 

  24. Mahendra, J., L. Mahendra, V.M. Kurian, K. Jaishankar, and R. Mythilli. 2010. 16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque. Indian journal of dental research : official publication of Indian Society for Dental Research 21 (2): 248–252. doi:10.4103/0970-9290.66649.

    Article  Google Scholar 

  25. Wang, Q., X. Zhou, and D. Huang. 2009. Role for Porphyromonas gingivalis in the progression of atherosclerosis. Medical Hypotheses 72 (1): 71–73. doi:10.1016/j.mehy.2008.04.030.

    Article  CAS  PubMed  Google Scholar 

  26. Shaddox, L.M., P.F. Goncalves, A. Vovk, N. Allin, H. Huang, W. Hou, I. Aukhil, and S.M. Wallet. 2013. LPS-induced inflammatory response after therapy of aggressive periodontitis. Journal of Dental Research 92 (8): 702–708. doi:10.1177/0022034513495242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gibson, F.C. 3rd, T. Ukai, and C.A. Genco. 2008. Engagement of specific innate immune signaling pathways during Porphyromonas gingivalis induced chronic inflammation and atherosclerosis. Frontiers in bioscience : a journal and virtual library 13: 2041–2059.

    Article  CAS  Google Scholar 

  28. Hajishengallis, G., H. Sojar, R.J. Genco, and E. DeNardin. 2004. Intracellular signaling and cytokine induction upon interactions of Porphyromonas gingivalis fimbriae with pattern-recognition receptors. Immunological Investigations 33 (2): 157–172.

    Article  CAS  PubMed  Google Scholar 

  29. Bugueno, I.M., Y. Khelif, N. Seelam, D.N. Morand, H. Tenenbaum, J.L. Davideau, and O. Huck. 2016. Porphyromonas gingivalis differentially modulates cell death profile in ox-LDL and TNF-alpha pre-treated endothelial cells. PloS One 11 (4): e0154590. doi:10.1371/journal.pone.0154590.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Huang, C.Y., C.M. Shih, N.W. Tsao, Y.W. Lin, C.C. Shih, K.H. Chiang, S.K. Shyue, Y.J. Chang, C.K. Hsieh, and F.Y. Lin. 2016. The GroEL protein of Porphyromonas gingivalis regulates atherogenic phenomena in endothelial cells mediated by upregulating toll-like receptor 4 expression. American Journal of Translational Research 8 (2): 384–404.

    PubMed  PubMed Central  Google Scholar 

  31. Gitlin, J.M., and C.D. Loftin. 2009. Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice. Cardiovascular Research 81 (2): 400–407. doi:10.1093/cvr/cvn286.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou, L., Z. Zuo, and M.S. Chow. 2005. Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. Journal of Clinical Pharmacology 45 (12): 1345–1359. doi:10.1177/0091270005282630.

    Article  CAS  PubMed  Google Scholar 

  33. Zhou, G.Y., B.L. Zhao, J.W. Hou, G.E. Ma, and W.J. Xin. 1999. Protective effects of sodium tanshinone IIA sulphonate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro. Pharmacological Research 40 (6): 487–491. doi:10.1006/phrs.1999.0545.

    Article  CAS  PubMed  Google Scholar 

  34. Tasly Pharmaceuticals, Inc. 2012. Phase III Trial of Dantonic® (T89) Capsule to Prevent and Treat Stable Angina (CAESA). http://clinicaltrials.gov/ct2/show/NCT01659580?term=Tasly&rank=3. Accessed 7 March 2017.

  35. Ju, H., W.L. Cheng, and X. Dong. 2005. Effect of salvia miltiorrhiza on the expression of matrix metalloproteinase 9 and intercellular adhesive moleculer-1 induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells. Journal of China-Japan Friendship Hospital 19 (4): 230–232.

    Google Scholar 

  36. Chen, W., F. Tang, B. Xie, S. Chen, H. Huang, and P. Liu. 2012. Amelioration of atherosclerosis by tanshinone IIA in hyperlipidemic rabbits through attenuation of oxidative stress. European Journal of Pharmacology 674 (2–3): 359–364. doi:10.1016/j.ejphar.2011.10.040.

    Article  CAS  PubMed  Google Scholar 

  37. Jia, L.Q., N. Zhang, Y. Xu, W.N. Chen, M.L. Zhu, N. Song, L. Ren, H.M. Cao, J.Y. Wang, and G.L. Yang. 2016. Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol. Archives of Biochemistry and Biophysics 592: 50–59. doi:10.1016/j.abb.2016.01.001.

    Article  CAS  PubMed  Google Scholar 

  38. Ye, J., and R.A. DeBose-Boyd. 2011. Regulation of cholesterol and fatty acid synthesis. Cold Spring Harbor Perspectives in Biology 3 (7). doi:10.1101/cshperspect.a004754.

  39. Li, L., N. Roumeliotis, T. Sawamura, and G. Renier. 2004. C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: Relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction. Circulation Research 95 (9): 877–883. doi:10.1161/01.RES.0000147309.54227.42.

    Article  CAS  PubMed  Google Scholar 

  40. Xu, S., S. Ogura, J. Chen, P.J. Little, J. Moss, and P. Liu. 2013. LOX-1 in atherosclerosis: Biological functions and pharmacological modifiers. Cellular and molecular life sciences : CMLS 70 (16): 2859–2872. doi:10.1007/s00018-012-1194-z.

    Article  CAS  PubMed  Google Scholar 

  41. Jang, S.I., S.I. Jeong, K.J. Kim, H.J. Kim, H.H. Yu, R. Park, H.M. Kim, and Y.O. You. 2003. Tanshinone IIA from Salvia miltiorrhiza inhibits inducible nitric oxide synthase expression and production of TNF-alpha, IL-1beta and IL-6 in activated RAW 264.7 cells. Planta Medica 69 (11): 1057–1059. doi:10.1055/s-2003-45157.

    Article  CAS  PubMed  Google Scholar 

  42. Jang, S.I., H.J. Kim, Y.J. Kim, S.I. Jeong, and Y.O. You. 2006. Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells: Possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. European Journal of Pharmacology 542 (1–3): 1–7. doi:10.1016/j.ejphar.2006.04.044.

    Article  CAS  PubMed  Google Scholar 

  43. Ling, S., A. Dai, Z. Guo, and P.A. Komesaroff. 2008. A preparation of herbal medicine Salvia miltiorrhiza reduces expression of intercellular adhesion molecule-1 and development of atherosclerosis in apolipoprotein E-deficient mice. Journal of Cardiovascular Pharmacology 51 (1): 38–44. doi:10.1097/FJC.0b013e31815a9575.

    Article  CAS  PubMed  Google Scholar 

  44. Xu, S., P.J. Little, T. Lan, Y. Huang, K. Le, X. Wu, X. Shen, H. Huang, Y. Cai, F. Tang, H. Wang, and P. Liu. 2011. Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in apolipoprotein-E knockout mice fed a high cholesterol diet. Archives of Biochemistry and Biophysics 515 (1–2): 72–79. doi:10.1016/j.abb.2011.08.006.

    Article  CAS  PubMed  Google Scholar 

  45. Lin, R., W.R. Wang, J.T. Liu, G.D. Yang, and C.J. Han. 2006. Protective effect of tanshinone IIA on human umbilical vein endothelial cell injured by hydrogen peroxide and its mechanism. Journal of Ethnopharmacology 108 (2): 217–222. doi:10.1016/j.jep.2006.05.004.

    Article  CAS  PubMed  Google Scholar 

  46. Kang, B.Y., S.W. Chung, S.H. Kim, S.Y. Ryu, and T.S. Kim. 2000. Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacology 49 (3): 355–361.

    Article  CAS  PubMed  Google Scholar 

  47. Galis, Z.S., and J.J. Khatri. 2002. Matrix metalloproteinases in vascular remodeling and atherogenesis: The good, the bad, and the ugly. Circulation Research 90 (3): 251–262.

    CAS  PubMed  Google Scholar 

  48. Pasterkamp, G., A.H. Schoneveld, D.J. Hijnen, D.P. de Kleijn, H. Teepen, A.C. van der Wal, and C. Borst. 2000. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery. Atherosclerosis 150 (2): 245–253.

    Article  CAS  PubMed  Google Scholar 

  49. Fang, Z.Y., R. Lin, B.X. Yuan, Y. Liu, and H. Zhang. 2007. Tanshinone IIA inhibits atherosclerotic plaque formation by down-regulating MMP-2 and MMP-9 expression in rabbits fed a high-fat diet. Life Sciences 81 (17–18): 1339–1345. doi:10.1016/j.lfs.2007.08.043.

    Article  CAS  PubMed  Google Scholar 

  50. Fang, J., S.W. Xu, P. Wang, F.T. Tang, S.G. Zhou, J. Gao, J.W. Chen, H.Q. Huang, and P.Q. Liu. 2010. Tanshinone II-A attenuates cardiac fibrosis and modulates collagen metabolism in rats with renovascular hypertension. Phytomedicine : international journal of phytotherapy and phytopharmacology 18 (1): 58–64. doi:10.1016/j.phymed.2010.06.002.

    Article  CAS  Google Scholar 

  51. Taganov, K.D., M.P. Boldin, K.J. Chang, and D. Baltimore. 2006. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences of the United States of America 103 (33): 12481–12486. doi:10.1073/pnas.0605298103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cheng, H.S., N. Sivachandran, A. Lau, E. Boudreau, J.L. Zhao, D. Baltimore, P. Delgado-Olguin, M.I. Cybulsky, and J.E. Fish. 2013. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Molecular Medicine 5 (7): 1017–1034. doi:10.1002/emmm.201202318.

    Article  PubMed  Google Scholar 

  53. Li, X., D. Kong, H. Chen, S. Liu, H. Hu, T. Wu, J. Wang, W. Chen, Y. Ning, Y. Li, and Z. Lu. 2016. miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1. Scientific reports 6: 21789. doi:10.1038/srep21789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. O'Connell, R.M., K.D. Taganov, M.P. Boldin, G. Cheng, and D. Baltimore. 2007. MicroRNA-155 is induced during the macrophage inflammatory response. Proceedings of the National Academy of Sciences of the United States of America 104 (5): 1604–1609. doi:10.1073/pnas.0610731104.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Gao, Y., J. Peng, Z. Ren, N.Y. He, Q. Li, X.S. Zhao, M.M. Wang, H.Y. Wen, Z.H. Tang, Z.S. Jiang, G.X. Wang, and L.S. Liu. 2016. Functional regulatory roles of microRNAs in atherosclerosis. Clinica chimica acta; international journal of clinical chemistry 460: 164–171. doi:10.1016/j.cca.2016.06.044.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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The Institutional Animal Care and Use Committee of Peking University Health Science Center approved all the animal protocols (approval number LA201464).

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The datasets supporting the conclusions of this article are included within the article and its additional files.

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Authors and Affiliations

  1. Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

    Yan Xuan, Xiaoxuan Wang, Yu Cai & Qing Xian Luan

  2. Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

    Yan Xuan & Yu Cai

  3. Department of Pharmacology and Toxicology, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China

    Yue Gao & Hao Huang

  4. National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People’s Republic of China

    Yu Cai & Qing Xian Luan

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  1. Yan Xuan
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Contributions

Y. X, Y. G, and QX. L designed and conducted the research. Y. X and Y. C provided essential reagents and materials. Y. X, H.H, and XX.W analyzed the data. Y. X, Y. C, and QX. L wrote the paper. Y. C and QX. L had primary responsibility for the final content and contributed equally. All authors have read and approved the final manuscript. The authors thank Dr. ZhiBin Chen for her kind assistance.

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Correspondence to Yu Cai or Qing Xian Luan.

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The authors declare that they have no competing interests.

Funding

This study was supported by grants from the National Natural Science Foundation of China (no. 81271148; no. 8140030482).

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QingXian Luan and Yu Cai contributed equally.

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Xuan, Y., Gao, Y., Huang, H. et al. Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis . Inflammation 40, 1631–1642 (2017). https://doi.org/10.1007/s10753-017-0603-8

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