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The Exosome-Derived Biomarker in Atherosclerosis and Its Clinical Application

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Exosomes are now accepted as potential biomarkers in cardiovascular disease development, especially in atherosclerosis. Atherosclerosis is a leading cause of cardiovascular disease-related death and morbidity, accounting for one-fifth of all deaths globally. Therefore, the biomarkers for the management of atherosclerosis is urgently needed. Exosomes are reported to play key roles cell-to-cell communication in atherosclerosis with lipid bilayer membranous vesicles containing nucleic acids, proteins, and lipid contents, which are released from all most of multiple kinds of living cells. This review aims to discuss the potential roles of exosome-derived miRNA, protein, and DNA as biomarkers in atherosclerosis pathogenesis, diagnosis, and therapy.

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References

  1. Huber, H. J., & Holvoet, P. (2015). Exosomes: Emerging roles in communication between blood cells and vascular tissues during atherosclerosis. Current Opinion in Lipidology, 26, 412–419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hao, X., & Fan, H. (2017). Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. European Review for Medical and Pharmacological Sciences, 21, 2725–2733.

    PubMed  Google Scholar 

  3. Yin, M., Loyer, X., & Boulanger, C. M. (2015). Extracellular vesicles as new pharmacological targets to treat atherosclerosis. European Journal of Pharmacology, 763, 90–103.

    Article  CAS  PubMed  Google Scholar 

  4. Chistiakov, D. A., Orekhov, A. N., & Bobryshev, Y. V. (2015). Extracellular vesicles and atherosclerotic disease. Cellular and Molecular Life Sciences, 72, 2697–2708.

    Article  CAS  PubMed  Google Scholar 

  5. Ailawadi, S., Wang, X., Gu, H., & Fan, G.-C. (2015). Pathologic function and therapeutic potential of exosomes in cardiovascular disease. Biochimica et Biophysica Acta, 1852, 1–11.

    Article  CAS  PubMed  Google Scholar 

  6. Alvarez-Llamas, G., Cuesta Fdl, G. M. E., Barderas, V., Darde, L. R. P., & Vivanco, F. (2008). Recent advances in atherosclerosis-based proteomics: New biomarkers and a future perspective. Expert Review Proteomics, 5, 679–691.

    Article  CAS  PubMed  Google Scholar 

  7. de Jong, O. G., Verhaar, M. C., Chen, Y., Vader, P., Gremmels, H., Posthuma, G., Schiffelers, R. M., Gucek, M., & van Balkom, B. W. (2012). Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. Journal of Extracellular Vesicles, 1, 18396. https://doi.org/10.3402/jev.v1i0.18396.

    Article  CAS  Google Scholar 

  8. Wolf, P. (1967). The nature and significance of platelet products in human plasma. British Journal of Haematology, 13, 269–288.

    Article  CAS  PubMed  Google Scholar 

  9. Hessvik, N. P., & Llorente, A. (2018). Current knowledge on exosome biogenesis and release. Cellular and Molecular Life Sciences, 75, 193–208.

    Article  CAS  PubMed  Google Scholar 

  10. Bretz, N. P., Ridinger, J., Rupp, A. K., Rimbach, K., Keller, S., Rupp, C., Marme, F., Umansky, L., Umansky, V., Eigenbrod, T., Sammar, M., & Altevogt, P. (2013). Body fluid exosomes promote secretion of inflammatory cytokines in monocytic cells via toll-like receptor signaling. The Journal of Biological Chemistry, 288, 36691–36702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Emanueli, C., Shearn, A. I. U., Angelini, G. D., & Sahoo, S. (2015). Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascular Pharmacology, 71, 24–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Khalyfa, A., & Gozal, D. (2014). Exosomal miRNAs as potential biomarkers of cardiovascular risk in children. Journal of Translational Medicine, 12, 162. https://doi.org/10.1186/1479-5876-12-162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ge, Q., Zhou, Y., Lu, J., Bai, Y., Xie, X., & Lu, Z. (2014). miRNA in plasma exosome is stable under different storage conditions. Molecules, 19, 1568–1575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Packard, R. R., & Libby, P. (2008). Inflammation in atherosclerosis: From vascular biology to biomarker discovery and risk prediction. Clinical Chemistry, 54, 24–38.

    Article  CAS  PubMed  Google Scholar 

  15. Izarra, A., Moscoso, I., Levent, E., Cañón, S., Cerrada, I., Díez-Juan, A., Blanca, V., Núñez-Gil, I.-J., Valiente, I., Ruíz-Sauri, A., Sepúlveda, P., Tiburcy, M., Zimmermann, W.-H., & Bernad, A. (2014). miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Reports, 3, 1029–1042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hergenreider, E., Heydt, S., Tréguer, K., Boettger, T., Horrevoets, A. J. G., Zeiher, A. M., Scheffer, M. P., Frangakis, A. S., Yin, X., Mayr, M., Braun, T., Urbich, C., Boon, R. A., & Dimmeler, S. (2012). Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature Cell Biology, 14, 249–256.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., Sun, F., Lu, J., Yin, Y., Cai, X., Sun, Q., Wang, K., Ba, Y., Wang, Q., Wang, D., Yang, J., Liu, P., Xu, T., Yan, Q., Zhang, J., Zen, K., & Zhang, C. Y. (2010). Secreted monocytic miR-150 enhances targeted endothelial cell migration. Molecular Cell, 39, 133–144.

    Article  CAS  PubMed  Google Scholar 

  18. Zheng, B., Yin, W. N., Suzuki, T., Zhang, X. H., Zhang, Y., Song, L. L., Jin, L. S., Zhan, H., Zhang, H., Li, J. S., & Wen, J. K. (2017). Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis. Molecular Therapy, 25, 1279–1294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. van Balkom, B. W., de Jong, O. G., Smits, M., Brummelman, J., den Ouden, K., de Bree, P. M., van Eijndhoven, M. A., Pegtel, D. M., Stoorvogel, W., Wurdinger, T., & Verhaar, M. C. (2013). Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood, 121, 3997–4006.

    Article  CAS  PubMed  Google Scholar 

  20. Ismail, N., Wang, Y., Dakhlallah, D., Moldovan, L., Agarwal, K., Batte, K., Shah, P., Wisler, J., Eubank, T. D., Tridandapani, S., Paulaitis, M. E., Piper, M. G., & Marsh, C. B. (2013). Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood, 121, 984–995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tan, M., Yan, H. B., Li, J. N., Li, W. K., Fu, Y. Y., Chen, W., & Zhou, Z. (2016). Thrombin stimulated platelet-derived exosomes inhibit platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells. Cellular Physiology and Biochemistry, 38, 2348–2365.

    Article  CAS  PubMed  Google Scholar 

  22. Gidlof, O., van der Brug, M., Ohman, J., Gilje, P., Olde, B., Wahlestedt, C., & Erlinge, D. (2013). Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM-1 expression. Blood, 121, 3908–3917.

    Article  CAS  PubMed  Google Scholar 

  23. Cervio, E., Barile, L., Moccetti, T., & Vassalli, G. (2015). Exosomes for Intramyocardial intercellular communication. Stem Cells International, 2015, 482171. https://doi.org/10.1155/2015/482171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cheng, C., Wang, Q., You, W., Chen, M., & Xia, J. (2014). MiRNAs as biomarkers of myocardial infarction: A meta-analysis. PLoS One, 9, e88566. https://doi.org/10.1371/journal.pone.0088566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Neppl, R. L., & Wang, D.-Z. (2014). The myriad essential roles of microRNAs in cardiovascular homeostasis and disease. Genes & Diseases, 1, 18–39.

    Article  CAS  Google Scholar 

  26. Hulsmans, M., & Holvoet, P. (2013). MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease. Cardiovascular Research, 100, 7–18.

    Article  CAS  PubMed  Google Scholar 

  27. Matkovich, S. J., Wang, W., Tu, Y., Eschenbacher, W. H., Dorn, L. E., Condorelli, G., Diwan, A., Nerbonne, J. M., & Dorn II, G. W. (2010). MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circulation Research, 106, 166–175.

    Article  CAS  PubMed  Google Scholar 

  28. Gao, S., Wassler, M., Zhang, L., Li, Y., Wang, J., Zhang, Y., Shelat, H., Williams, J., & Geng, Y. J. (2014). MicroRNA-133a regulates insulin-like growth factor-1 receptor expression and vascular smooth muscle cell proliferation in murine atherosclerosis. Atherosclerosis, 232, 171–179.

    Article  CAS  PubMed  Google Scholar 

  29. Zhao, Y., Li, Y., Luo, P., Gao, Y., Yang, J., Lao, K. H., Wang, G., Cockerill, G., Hu, Y., Xu, Q., Li, T., & Zeng, L. (2016). XBP1 splicing triggers miR-150 transfer from smooth muscle cells to endothelial cells via extracellular vesicles. Scientific Reports, 6, 28627. https://doi.org/10.1038/srep28627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pan, Y., Liang, H., Liu, H., Li, D., Chen, X., Li, L., Zhang, C. Y., & Zen, K. (2013). Platelet-secreted microRNA-223 promotes endothelial cell apoptosis induced by advanced glycation end products via targeting the insulin-like growth factor 1 receptor. The Journal of Immunology, 192, 437–446.

    Article  CAS  PubMed  Google Scholar 

  31. Jiang, M., Jing, Q., Zhang, H., Ding, Q. Q., Xiang, M., Meng, D., Sun, N., & Chen, S. F. (2016). Proteomic identification of proteins in exosomes of patients with atherosclerosis. Chinese Journal Pathophysiology, 24, 1525–1526.

    Google Scholar 

  32. Chyrchel, B., Toton-Zuranska, J., Kruszelnicka, O., Chyrchel, M., Mielecki, W., Kolton-Wroz, M., Wolkow, P., & Surdacki, A. (2015). Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: A preliminary report. Platelets, 26, 593–597.

    Article  CAS  PubMed  Google Scholar 

  33. Tang, N., Sun, B., Gupta, A., Rempel, H., & Pulliam, L. (2016). Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-kappaB in endothelial cells. FASEB Journal, 30, 3097–3106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Niu, C., Wang, X., Zhao, M., Cai, T., Liu, P., Li, J., Willard, B., Zu, L., Zhou, E., Li, Y., Pan, B., Yang, F., & Zheng, L. (2016). Macrophage foam cell-derived extracellular vesicles promote vascular smooth muscle cell migration and adhesion. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.116.004099.

  35. Goetzl, E. J., Schwartz, J. B., Mustapic, M., Lobach, I. V., Daneman, R., Abner, E. L., & Jicha, G. A. (2017). Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease. FASEB Journal, 31, 3689–3694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zheng, X., Chen, F., Zhang, Q., Liu, Y., You, P., Sun, S., Lin, J., & Chen, N. (2017). Salivary exosomal PSMA7: A promising biomarker of inflammatory bowel disease. Protein & Cell, 8, 686–695.

    Article  CAS  Google Scholar 

  37. Cai, J., Han, Y., Ren, H., Chen, C., He, D., Zhou, L., Eisner, G. M., Asico, L. D., Jose, P. A., & Zeng, C. (2013). Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. Journal of Molecular Cell Biology, 5, 227–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cai, J., Guan, W., Tan, X., Chen, C., Li, L., Wang, N., Zou, X., Zhou, F., Wang, J., Pei, F., Chen, X., Luo, H., Wang, X., He, D., Zhou, L., Jose, P. A., & Zeng, C. (2015). SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells. Clinical Science, 129, 259–269.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Mengmeng Lu and Shuaifang Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of Hypertension, Henan Provincial People’s Hospital, Laboratory of Cancer Biomarkers and Liquid Biopsy, Henan University, Kaifeng, Henan Province, 475004, China

    Mengmeng Lu, Shuaifang Yuan, Ling Li & Min Liu

  2. Laboratory of Cancer Biomarkers and Liquid Biopsy, Henan University, Kaifeng, Henan Province, 475004, China

    Shicheng Li & Shaogui Wan

  3. Department of Hypertension, Henan Provincial People’s Hospital, Zhenzhou, Henan, 450003, China

    Min Liu

  4. Institute of Biomedical Informatics, Medical School, Henan University, Kaifeng, Henan Province, 475004, China

    Shaogui Wan

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  1. Mengmeng Lu
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  2. Shuaifang Yuan
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  3. Shicheng Li
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  4. Ling Li
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  5. Min Liu
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Correspondence to Min Liu or Shaogui Wan.

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The authors declare that they have no conflict of interest. This review article does not contain any studies with human participants or animals performed by any of authors.

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Associate Editor Junjie Xiao oversaw the review of this article

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Lu, M., Yuan, S., Li, S. et al. The Exosome-Derived Biomarker in Atherosclerosis and Its Clinical Application. J. of Cardiovasc. Trans. Res. 12, 68–74 (2019). https://doi.org/10.1007/s12265-018-9796-y

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  • DOI: https://doi.org/10.1007/s12265-018-9796-y

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