本研究旨在综述外泌体在心血管疾病中的研究进展,为完善细胞治疗在心血管疾病中的机制提供理论基础。外泌体是多种细胞在一定条件下分泌的微小囊泡,直径在30~150 nm,外泌体中包含了丰富的蛋白质、脂质与核酸。近几年的研究发现外泌体可参与心血管疾病的发生发展,在心血管疾病诊断和治疗中发挥重要的作用。外泌体可以通过影响细胞增殖、凋亡和自噬,调节相关细胞微环境,促进血管的新生等多方面促进心血管疾病的发生与发展。外泌体还可以作为心血管疾病的生物标志物,作为心血管疾病的治疗靶点等。本文就外泌体的形成、组成和功能以及近几年外泌体在心血管疾病中的作用进行综述。
Exosomes are micro-vesicles secreted by a variety of cells under certain conditions, ranging in diameter from 30 to 150 nm. The exosomes contain abundant proteins, lipids and nucleic acids. In recent years, studies have found that exosomes can participate in the development of cardiovas-cular diseases and play an important role in diagnosis and treatment of cardiovascular diseases. Exosomes can promote the occurrence and development of cardiovascular diseases by affecting cell proliferation, apoptosis and autophagy, regulating the relevant cellular microenvironment, and promoting the regeneration of blood vessels. Exosomes can also be used as biomarkers for cardiovascular diseases, as therapeutic targets for cardiovascular diseases. This article reviews the formation, composition and function of exosomes and the role of exosomes in cardiovascular disease in recent years.
程 灏,骆晨涛,马剑英. 外泌体在心血管疾病中的研究进展 Research Progress of Exosomes in Cardiovascular Diseases[J]. 临床医学进展, 2019, 09(01): 42-50. https://doi.org/10.12677/ACM.2019.91009
参考文献ReferencesZhao, W., Zheng, X.L. and Zhao, S.P. (2015) Exosome and Its Roles in Cardiovascular Diseases. Heart Failure Reviews, 20, 337-348. <br>https://doi.org/10.1007/s10741-014-9469-0Williams, A.R. and Hare, J.M. (2011) Mesenchymal Stem Cells: Biology, Pathophysiology, Translational Findings, and Therapeutic Implications for Cardiac Disease. Circulation Research, 109, 923-940.
<br>https://doi.org/10.1161/CIRCRESAHA.111.243147Jhund, P.S. and McMurray, J.J. (2008) Heart Failure after Acute Myocardial Infarction: A Lost Battle in the War on Heart Failure? Circulation, 118, 2019-2021. <br>https://doi.org/10.1161/CIRCULATIONAHA.108.813493Ibrahim, A.G.E., Cheng, K. and Marban, E. (2014) Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy. Stem Cell Reports, 2, 606-619. <br>https://doi.org/10.1016/j.stemcr.2014.04.006Yellon, D.M. and Davidson, S.M. (2014) Exosomes: Nanoparticles Involved in Cardioprotection? Circulation Research, 114, 325-332. <br>https://doi.org/10.1161/CIRCRESAHA.113.300636Raposo, G. and Stoorvogel, W. (2013) Extracellular Vesicles: Exosomes, Microvesicles, and Friends. Journal of Cell Biology, 200, 373-383. <br>https://doi.org/10.1083/jcb.201211138Nana-Sinkam, S.P., Acunzo, M., Croce, C.M. and Wang, K. (2017) Extracellular Vesicle Biology in the Pathogenesis of Lung Disease. American Journal of Respiratory and Critical Care Medicine, 196, 1510-1518.
<br>https://doi.org/10.1164/rccm.201612-2457PPZhou, L., Lv, T., Zhang, Q., Zhu, Q., Zhan, P., Zhu, S., Zhang, J. and Song, Y. (2017) The Biology, Function and Clinical Implications of Exosomes in Lung Cancer. Cancer Letters, 407, 84-92.
<br>https://doi.org/10.1016/j.canlet.2017.08.003De Toro, J., Herschlik, L., Waldner, C. and Mongini, C. (2015) Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications. Frontiers in Immunology, 6, 203.
<br>https://doi.org/10.3389/fimmu.2015.00203Mathivanan, S., Ji, H. and Simpson, R.J. (2010) Exosomes: Extracellular Organelles Important in Intercellular Communication. Journal of Proteomics, 73, 1907-1920. <br>https://doi.org/10.1016/j.jprot.2010.06.006Dragovic, R.A., Gardiner, C., Brooks, A.S., Tannetta, D.S., Ferguson, D.J.P., Hole, P., Carr, B., Redman, C.W.G., Harris, A.L., Dobson, P.J., Harrison, P. and Sargent, I.L. (2011) Sizing and Phenotyping of Cellular Vesicles Using Nanoparticle Tracking Analysis. Nanomedicine: Nanotechnology, Biology and Medicine, 7, 780-788.
<br>https://doi.org/10.1016/j.nano.2011.04.003Lasser, C., Alikhani, V.S., Ekstrom, K., Eldh, M., Paredes, P.T., Bossios, A., Sjostrand, M., Gabrielsson, S., Lotvall, J. and Valadi, H. (2011) Human Saliva, Plasma and Breast Milk Exosomes Contain RNA: Uptake by Macrophages. Journal of Translational Medicine, 9, 9. <br>https://doi.org/10.1186/1479-5876-9-9Zhang, B., Yin, Y., Lai, R.C., Tan, S.S., Choo, A.B. and Lim, S.K. (2014) Mesenchymal Stem Cells Secrete Immunologically Active Exosomes. Stem Cells and Development, 23, 1233-1244. <br>https://doi.org/10.1089/scd.2013.0479Zhou, Y., Xu, H., Xu, W., Wang, B., Wu, H., Tao, Y., Zhang, B., Wang, M., Mao, F., Yan, Y., Gao, S., Gu, H., Zhu, W. and Qian, H. (2013) Exosomes Released by Human Umbilical Cord Mesenchymal Stem Cells Protect against Cisplatin-Induced Renal Oxidative Stress and Apoptosis in Vivo and in Vitro. Stem Cell Research & Therapy, 4, 34.
<br>https://doi.org/10.1186/scrt194Kogure, T., Lin, W.L., Yan, I.K., Braconi, C. and Patel, T. (2011) Intercellular Nanovesicle-Mediated MicroRNA Transfer: A Mechanism of Environmental Modulation of Hepatocellular Cancer Cell Growth. Hepatology, 54, 1237-1248. <br>https://doi.org/10.1002/hep.24504Shin, S.J., Smith, J.A., Rezniczek, G.A., Pan, S., Chen, R., Brentnall, T.A., Wiche, G. and Kelly, K.A. (2013) Unexpected Gain of Function for the Scaffolding Protein Plectin Due to Mislocalization in Pancreatic Cancer. Proceedings of the National Academy of Sciences of the United States of America, 110, 19414-19419.
<br>https://doi.org/10.1073/pnas.1309720110Llorente, A., Skotland, T., Sylvanne, T., Kauhanen, D., Rog, T., Orlowski, A., Vattulainen, I., Ekroos, K. and Sandvig, K. (2013) Molecular Lipidomics of Exosomes Released by PC-3 Prostate Cancer Cells. Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, 1831, 1302-1309. <br>https://doi.org/10.1016/j.bbalip.2013.04.011Zhang, H.G. (2016) Exosomes: A Novel Pathway of Local and Distant Intercellular Communication That Facilitates the Growth and Metastasis of Neoplastic Lesions. The American Journal of Pathology, 186, 1710-1710.Pant, S., Hilton, H. and Burczynski, M.E. (2012) The Multifaceted Exosome: Biogenesis, Role in Normal and Aberrant Cellular Function, and Frontiers for Pharmacological and Biomarker Opportunities. Biochemical Pharmacology, 83, 1484-1494. <br>https://doi.org/10.1016/j.bcp.2011.12.037Colombo, M., Raposo, G. and Thery, C. (2014) Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles. Annual Review of Cell and Developmental Biology, 30, 255-289.
<br>https://doi.org/10.1146/annurev-cellbio-101512-122326Sahoo, S., Klychko, E., Thorne, T., Misener, S., Schultz, K.M., Millay, M., Ito, A., Liu, T., Kamide, C., Agrawal, H., Perlman, H., Qin, G.J., Kishore, R. and Losordo, D.W. (2011) Exosomes from Human CD34(+) Stem Cells Mediate Their Proangiogenic Paracrine Activity. Circulation Research, 109, 724-U735.
<br>https://doi.org/10.1161/CIRCRESAHA.111.253286Khan, M., Nickoloff, E., Abramova, T., Johnson, J., Verma, S.K., Krishnamurthy, P., Mackie, A.R., Vaughan, E., Garikipati, V.N.S., Benedict, C., Ramirez, V., Lambers, E., Ito, A., Gao, E., Misener, S., Luongo, T., Elrod, J., Qin, G.J., Houser, S.R., Koch, W.J. and Kishore, R. (2015) Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction. Circulation Research, 117, 52-64.Garcia, N.A., Ontoria-Oviedo, I., Gonzalez-King, H., Diez-Juan, A. and Sepulveda, P. (2015) Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells. PLoS ONE, 10, e0138849. <br>https://doi.org/10.1371/journal.pone.0138849Li, X.C., Chen, C.Y., Wei, L.M., Li, Q., Niu, X., Xu, Y.J., Wang, Y. and Zhao, J.G. (2016) Exosomes Derived from Endothelial Progenitor Cells Attenuate Vascular Repair and Accelerate Reendothelialization by Enhancing Endothelial Function. Cytotherapy, 18, 253-262. <br>https://doi.org/10.1016/j.jcyt.2015.11.009Barile, L., Lionetti, V., Cervio, E., Matteucci, M., Gherghiceanu, M., Popescu, L.M., Torre, T., Siclari, F., Moccetti, T. and Vassalli, G. (2014) Extracellular Vesicles from Human Cardiac Progenitor Cells Inhibit Cardiomyocyte Apoptosis and Improve Cardiac Function after Myocardial Infarction. Cardiovascular Research, 103, 530-541.
<br>https://doi.org/10.1093/cvr/cvu167Taylor, D.D. and Shah, S. (2015) Methods of Isolating Extracellular Vesicles Impact Down-Stream Analyses of Their Cargoes. Methods, 87, 3-10. <br>https://doi.org/10.1016/j.ymeth.2015.02.019Nozaki, T., Sugiyama, S., Koga, H., Sugamura, K., Ohba, K., Matsuzawa, Y., Sumida, H., Matsui, K., Jinnouchi, H. and Ogawa, H. (2009) Significance of a Multiple Biomarkers Strategy Including Endothelial Dysfunction to Improve Risk Stratification for Cardiovascular Events in Patients at High Risk for Coronary Heart Disease. Journal of the American College of Cardiology, 54, 601-608. <br>https://doi.org/10.1016/j.jacc.2009.05.022Amabile, N., Cheng, S., Renard, J.M., Larson, M.G., Ghorbani, A., McCabe, E., Griffin, G., Guerin, C., Ho, J.E., Shaw, S.Y., Cohen, K.S., Vasan, R.S., Tedgui, A., Boulanger, C.M. and Wang, T.J. (2014) Association of Circulating Endothelial Microparticles with Cardiometabolic Risk Factors in the Framingham Heart Study. European Heart Journal, 35, 2972-2979. <br>https://doi.org/10.1093/eurheartj/ehu153Montecalvo, A., Larregina, A.T., Shufesky, W.J., Stolz, D.B., Sullivan, M.L., Karlsson, J.M., Baty, C.J., Gibson, G.A., Erdos, G., Wang, Z., Milosevic, J., Tkacheva, O.A., Divito, S.J., Jordan, R., Lyons-Weiler, J., Watkins, S.C. and Morelli, A.E. (2012) Mechanism of Transfer of Functional microRNAs between Mouse Dendritic Cells via Exosomes. Blood, 119, 756-766. <br>https://doi.org/10.1182/blood-2011-02-338004Stoorvogel, W. (2012) Functional Transfer of microRNA by Exosomes. Blood, 119, 646-648.
<br>https://doi.org/10.1182/blood-2011-11-389478Sahoo, S. and Losordo, D.W. (2014) Exosomes and Cardiac Repair after Myocardial Infarction. Circulation Research, 114, 333-344. <br>https://doi.org/10.1161/CIRCRESAHA.114.300639Triggle, C.R., Samuel, S.M., Ravishankar, S., Marei, I., Arunachalam, G. and Ding, H. (2012) The Endothelium: Influencing Vascular Smooth Muscle in Many Ways. Canadian Journal of Physiology and Pharmacology, 90, 713-738.
<br>https://doi.org/10.1139/y2012-073Paik, D.T., Rai, M., Ryzhov, S., Sanders, L.N., Aisagbonhi, O., Funke, M.J., Feoktistov, I. and Hatzopoulos, A.K. (2015) Wnt10b Gain-of-Function Improves Cardiac Repair by Arteriole Formation and Attenuation of Fibrosis. Circulation Research, 117, 804-816. <br>https://doi.org/10.1161/CIRCRESAHA.115.306886Hergenreider, E., Heydt, S., Treguer, K., Boettger, T., Horrevoets, A.J., Zeiher, A.M., Scheffer, M.P., Frangakis, A.S., Yin, X., Mayr, M., Braun, T., Urbich, C., Boon, R.A. and Dimmeler, S. (2012) Atheroprotective Communication between Endothelial Cells and Smooth Muscle Cells through miRNAs. Nature Cell Biology, 14, 249-256.
<br>https://doi.org/10.1038/ncb2441Oerlemans, M.I., Mosterd, A., Dekker, M.S., de Very, E.A., van Mil, A., Pasterkamp, G., Doevendans, P.A., Hoes, A.W. and Sluijter, J.P. (2012) Early Assessment of Acute Coronary Syndromes in the Emergency Department: The Potential Diagnostic Value of Circulating microRNAs. EMBO Molecular Medicine, 4, 1176-1185.
<br>https://doi.org/10.1002/emmm.201201749Jansen, F., Yang, X., Proebsting, S., Hoelscher, M., Przybilla, D., Baumann, K., Schmitz, T., Dolf, A., Endl, E., Franklin, B.S., Sinning, J.M., Vasa-Nicotera, M., Nickenig, G. and Werner, N. (2014) MicroRNA Expression in Circulating Microvesicles Predicts Cardiovascular Events in Patients with Coronary Artery Disease. Journal of the American Heart Association, 3, e001249. <br>https://doi.org/10.1161/JAHA.114.001249Matsumoto, S., Sakata, Y., Suna, S., Nakatani, D., Usami, M., Hara, M., Kitamura, T., Hamasaki, T., Nanto, S., Kawahara, Y. and Komuro, I. (2013) Circulating p53-Responsive microRNAs Are Predictive Indicators of Heart Failure after Acute Myocardial Infarction. Circulation Research, 113, 322-326.
<br>https://doi.org/10.1161/CIRCRESAHA.113.301209Madrigal-Matute, J., Lindholt, J.S., Fernandez-Garcia, C.E., Benito-Martin, A., Burillo, E., Zalba, G., Beloqui, O., Llamas-Granda, P., Ortiz, A., Egido, J., Blanco-Colio, L.M. and Martin-Ventura, J.L. (2014) Galectin-3, a Biomarker Linking Oxidative Stress and Inflammation with the Clinical Outcomes of Patients with Atherothrombosis. Journal of the American Heart Association, 3, e000785.Nouraee, N. and Mowla, S.J. (2015) miRNA Therapeutics in Cardiovascular Diseases: Promises and Problems. Frontiers in Genetics, 6, 232. <br>https://doi.org/10.3389/fgene.2015.00232O’Loughlin, A.J., Woffindale, C.A. and Wood, M.J. (2012) Exosomes and the Emerging Field of Exosome-Based Gene Therapy. Current Gene Therapy, 12, 262-274. <br>https://doi.org/10.2174/156652312802083594Lai, R.C., Arslan, F., Lee, M.M., Sze, N.S., Choo, A., Chen, T.S., Salto-Tellez, M., Timmers, L., Lee, C.N., El Oakley, R.M., Pasterkamp, G., de Kleijn, D.P. and Lim, S.K. (2010) Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury. Stem Cell Research, 4, 214-222. <br>https://doi.org/10.1016/j.scr.2009.12.003Martinez, M.C., Larbret, F., Zobairi, F., Coulombe, J., Debili, N., Vainchenker, W., Ruat, M. and Freyssinet, J.M. (2006) Transfer of Differentiation Signal by Membrane Microvesicles Harboring Hedgehog Morphogens. Blood, 108, 3012-3020. <br>https://doi.org/10.1182/blood-2006-04-019109Zhao, Y., Sun, X., Cao, W., Ma, J., Sun, L., Qian, H., Zhu, W. and Xu, W. (2015) Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury. Stem Cells International, 2015, Article ID: 761643. <br>https://doi.org/10.1155/2015/761643Yu, B., Kim, H.W., Gong, M., Wang, J., Millard, R.W., Wang, Y., Ashraf, M. and Xu, M. (2015) Exosomes Secreted from GATA-4 Overexpressing Mesenchymal Stem Cells Serve as a Reservoir of Anti-Apoptotic microRNAs for Cardioprotection. International Journal of Cardiology, 182, 349-360. <br>https://doi.org/10.1016/j.ijcard.2014.12.043Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., Zhu, Y., Wu, L., Pan, Z., Zhu, W., Qian, H. and Xu, W. (2015) Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis through the Wnt4/Beta-Catenin Pathway. Stem Cells Translational Medicine, 4, 513-522. <br>https://doi.org/10.5966/sctm.2014-0267Arslan, F., Lai, R.C., Smeets, M.B., Akeroyd, L., Choo, A., Aguor, E.N., Timmers, L., van Rijen, H.V., Doevendans, P.A., Pasterkamp, G., Lim, S.K. and de Kleijn, D.P. (2013) Mesenchymal Stem Cell-Derived Exosomes Increase ATP Levels, Decrease Oxidative Stress and Activate PI3K/Akt Pathway to Enhance Myocardial Viability and Prevent Adverse Remodeling after Myocardial Ischemia/Reperfusion Injury. Stem Cell Research, 10, 301-312.
<br>https://doi.org/10.1016/j.scr.2013.01.002Fu, X., Koller, S., Abd Alla, J. and Quitterer, U. (2013) Inhibition of G-Protein-Coupled Receptor Kinase 2 (GRK2) Triggers the Growth-Promoting Mitogen-Activated Protein Kinase (MAPK) Pathway. The Journal of Biological Chemistry, 288, 7738-7755. <br>https://doi.org/10.1074/jbc.M112.428078Gazdhar, A., Grad, I., Tamo, L., Gugger, M., Feki, A. and Geiser, T. (2014) The Secretome of Induced Pluripotent Stem Cells Reduces Lung Fibrosis in Part by Hepatocyte Growth Factor. Stem Cell Research & Therapy, 5, 123.
<br>https://doi.org/10.1186/scrt513Wang, Y., Zhang, L., Li, Y., Chen, L., Wang, X., Guo, W., Zhang, X., Qin, G., He, S.H., Zimmerman, A., Liu, Y., Kim, I.M., Weintraub, N.L. and Tang, Y. (2015) Exosomes/Microvesicles from Induced Pluripotent Stem Cells Deliver Cardioprotective miRNAs and Prevent Cardiomyocyte Apoptosis in the Ischemic Myocardium. International Journal of Cardiology, 192, 61-69. <br>https://doi.org/10.1016/j.ijcard.2015.05.020Bobis-Wozowicz, S., Kmiotek, K., Sekula, M., Kedracka-Krok, S., Kamycka, E., Adamiak, M., Jankowska, U., Madetko-Talowska, A., Sarna, M., Bik-Multanowski, M., Kolcz, J., Boruczkowski, D., Madeja, Z., Dawn, B. and Zuba-Surma, E.K. (2015) Human Induced Pluripotent Stem Cell-Derived Microvesicles Transmit RNAs and Proteins to Recipient Mature Heart Cells Modulating Cell Fate and Behavior. Stem Cells, 33, 2748-2761.
<br>https://doi.org/10.1002/stem.2078Zhou, J., Ghoroghi, S., Benito-Martin, A., Wu, H., Unachukwu, U.J., Einbond, L.S., Guariglia, S., Peinado, H. and Redenti, S. (2016) Characterization of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology and Pluripotent Content. Scientific Reports, 6, Article No. 19743. <br>https://doi.org/10.1038/srep19743Chong, J.J., Yang, X., Don, C.W., Minami, E., Liu, Y.W., Weyers, J.J., Mahoney, W.M., Van Biber, B., Cook, S.M., Palpant, N.J., Gantz, J.A., Fugate, J.A., Muskheli, V., Gough, G.M., Vogel, K.W., Astley, C.A., Hotchkiss, C.E., Baldessari, A., Pabon, L., Reinecke, H., Gill, E.A., Nelson, V., Kiem, H.P., Laflamme, M.A. and Murry, C.E. (2014) Human Embryonic-Stem-Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts. Nature, 510, 273-277.
<br>https://doi.org/10.1038/nature13233Parolini, I., Federici, C., Raggi, C., Lugini, L., Palleschi, S., De Milito, A., Coscia, C., Iessi, E., Logozzi, M., Molinari, A., Colone, M., Tatti, M., Sargiacomo, M. and Fais, S. (2009) Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells. The Journal of Biological Chemistry, 284, 34211-34222.
<br>https://doi.org/10.1074/jbc.M109.041152Caspi, O., Huber, I., Kehat, I., Habib, M., Arbel, G., Gepstein, A., Yankelson, L., Aronson, D., Beyar, R. and Gepstein, L. (2007) Transplantation of Human Embryonic Stem Cell-Derived Cardiomyocytes Improves Myocardial Performance in Infarcted Rat Hearts. Journal of the American College of Cardiology, 50, 1884-1893.
<br>https://doi.org/10.1016/j.jacc.2007.07.054Laflamme, M.A., Chen, K.Y., Naumova, A.V., Muskheli, V., Fugate, J.A., Dupras, S.K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., O’Sullivan, C., Collins, L., Chen, Y., Minami, E., Gill, E.A., Ueno, S., Yuan, C., Gold, J. and Murry, C.E. (2007) Cardiomyocytes Derived from Human Embryonic Stem Cells in Pro-Survival Factors Enhance Function of Infarcted Rat Hearts. Nature Biotechnology, 25, 1015-1024. <br>https://doi.org/10.1038/nbt1327Blin, G., Nury, D., Stefanovic, S., Neri, T., Guillevic, O., Brinon, B., Bellamy, V., Ruecker-Martin, C., Barbry, P., Bel, A., Bruneval, P., Cowan, C., Pouly, J., Mitalipov, S., Gouadon, E., Binder, P., Hagege, A., Desnos, M., Renaud, J.F., Menasche, P. and Puceat, M. (2010) A Purified Population of Multipotent Cardiovascular Progenitors Derived from Primate Pluripotent Stem Cells Engrafts in Postmyocardial Infarcted Nonhuman Primates. Journal of Clinical Investigation, 120, 1125-1139. <br>https://doi.org/10.1172/JCI40120Passier, R., van Laake, L.W. and Mummery, C.L. (2008) Stem-Cell-Based Therapy and Lessons from the Heart. Nature, 453, 322-329. <br>https://doi.org/10.1038/nature07040Alvarez-Erviti, L., Seow, Y.Q., Yin, H.F., Betts, C., Lakhal, S. and Wood, M.J.A. (2011) Delivery of siRNA to the Mouse Brain by Systemic Injection of Targeted Exosomes. Nature Biotechnology, 29, 341-U179.
<br>https://doi.org/10.1038/nbt.1807Wahlgren, J., Karlson, T.D., Brisslert, M., Sani, F.V., Telemo, E., Sunnerhagen, P. and Valadi, H. (2012) Plasma Exosomes Can Deliver Exogenous Short Interfering RNA to Monocytes and Lymphocytes. Nucleic Acids Research, 40, e130. <br>https://doi.org/10.1093/nar/gks463Khan, M., Nickoloff, E., Abramova, T., Johnson, J., Verma, S.K., Krishnamurthy, P., Mackie, A.R., Vaughan, E., Garikipati, V.N., Benedict, C., Ramirez, V., Lambers, E., Ito, A., Gao, E., Misener, S., Luongo, T., Elrod, J., Qin, G., Houser, S.R., Koch, W.J. and Kishore, R. (2015) Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction. Circulation Research, 117, 52-64.Xie, Z., Wang, X., Liu, X., Du, H., Sun, C., Shao, X., Tian, J., Gu, X., Wang, H., Tian, J. and Yu, B. (2018) Adipose-Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization. Journal of the American Heart Association, 7, e007442. <br>https://doi.org/10.1161/JAHA.117.007442Chen, Y., Zhao, Y., Chen, W., Xie, L., Zhao, Z.A., Yang, J., Chen, Y., Lei, W. and Shen, Z. (2017) MicroRNA-133 Overexpression Promotes the Therapeutic Efficacy of Mesenchymal Stem Cells on Acute Myocardial Infarction. Stem Cell Research & Therapy, 8, 268. <br>https://doi.org/10.1186/s13287-017-0722-zKomaki, M., Numata, Y., Morioka, C., Honda, I., Tooi, M., Yokoyama, N., Ayame, H., Iwasaki, K., Taki, A., Oshima, N. and Morita, I. (2017) Exosomes of Human Placenta-Derived Mesenchymal Stem Cells Stimulate Angiogenesis. Stem Cell Research & Therapy, 8, 219. <br>https://doi.org/10.1186/s13287-017-0660-9