Top

Journal of Cardiovascular Translational Research

Published in:

01-04-2020 | Arterial Occlusive Disease | Review

Extracellular Vesicles as Messengers in Atherosclerosis

Authors: Mengna Peng, Xinfeng Liu, Gelin Xu

Published in: Journal of Cardiovascular Translational Research | Issue 2/2020

Abstract

Atherosclerosis is a major cause of cardiovascular diseases. Most cells involved in atherosclerosis can shed extracellular vesicles (EVs). Both atherogenic factors, such as hypoxia and oxidative stress, and atheroprotective factors, such as laminar blood flow, can influence the production of EV shedding. EVs can carry protein, DNA, mRNA, and noncoding RNA and act as mediators or messengers for cell-to-cell communications. EVs have been proven to promote or inhibit atherogenesis under particular circumstances. Therefore, EVs might be targeted for preventing or treating atherosclerotic diseases. The level of circulating EVs has been associated with the presence, progressiveness, or severity of atherosclerosis. Therefore, EVs may be utilized as indexes for diagnosing and grading atherosclerosis. Here, we reviewed the progress concerning the involvements of EVs in atherogenesis and atheroprotection. We also discussed the potential applications of EVs in managing atherosclerotic diseases.

van der Pol, E., Boing, A. N., Harrison, P., Sturk, A., & Nieuwland, R. (2012). Classification, functions, and clinical relevance of extracellular vesicles. Pharmacological Reviews, 64(3), 676–705.PubMed

Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. Journal of Cell Biology, 200(4), 373-8(1540-8140 (Electronic)).

Zhang, J., Li, S., Li, L., Li, M., Guo, C., Yao, J., et al. (2015). Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics, Proteomics & Bioinformatics, 13(1), 17–24.

Boukouris, S., & Mathivanan, S. (2015). Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteomics. Clinical Applications, 9(3-4), 358–367.PubMedPubMedCentral

Morel, O., Jesel, L., Freyssinet, J. M., & Toti, F. (2011). Cellular mechanisms underlying the formation of circulating microparticles. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(1), 15–26.PubMed

Giuseppina Turturici, R. T., Sconzo, G., & Geraci, F. (2014). Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. American Journal of Physiology. Cell Physiology, 306, C621–CC33.PubMed

Brown, R. A., Shantsila, E., Varma, C., & Lip, G. Y. (2017). Current understanding of atherogenesis. The American Journal of Medicine, 130(3), 268–282.PubMed

Gao, W., Liu, H., Yuan, J., Wu, C., Huang, D., Ma, Y., et al. (2016). Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-alpha mediated NF-kappaB pathway. Journal of Cellular and Molecular Medicine, 20(12), 2318–2327.PubMedPubMedCentral

Zakharova, L., Svetlova, M., & Fomina, A. F. (2007). T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. Journal of Cellular Physiology, 212(1), 174–181.PubMed

10.

Jansen, F., Yang, X., Franklin, B. S., Hoelscher, M., Schmitz, T., Bedorf, J., et al. (2013). High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. Cardiovascular Research, 98(1), 94–106.PubMed

11.

Paudel, K. R., Panth, N., & Kim, D. W. (2016). Circulating endothelial microparticles: a key hallmark of atherosclerosis progression. Scientifica., 2016, 8514056.PubMedPubMedCentral

12.

Jansen, F., Yang, X., Hoelscher, M., Cattelan, A., Schmitz, T., Proebsting, S., et al. (2013). Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation., 128(18), 2026–2038.PubMed

13.

Jansen, F., Stumpf, T., Proebsting, S., Franklin, B. S., Wenzel, D., Pfeifer, P., et al. (2017). Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6. Journal of Molecular and Cellular Cardiology, 104, 43–52.PubMed

14.

Njock, M. S., Cheng, H. S., Dang, L. T., Nazari-Jahantigh, M., Lau, A. C., Boudreau, E., et al. (2015). Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing antiinflammatory microRNAs. Blood., 125(20), 3202–3212.PubMedPubMedCentral

15.

Keyel, P. A., Tkacheva, O. A., Larregina, A. T., & Salter, R. D. (2012). Coordinate stimulation of macrophages by microparticles and TLR ligands induces foam cell formation. Journal of Immunology, 189(9), 4621–4629.

16.

Barberio, M. D., Kasselman, L. J., Playford, M. P., Epstein, S. B., Renna, H. A., Goldberg, M., et al. (2019). Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs. Journal of Translational Medicine, 17(1).

17.

Lovren, F., & Verma, S. (2013). Evolving role of microparticles in the pathophysiology of endothelial dysfunction. Clinical Chemistry, 59(8), 1166–1174.PubMed

18.

Huang, C., Huang, Y., Zhou, Y., Nie, W., Pu, X., Xu, X., et al. (2018). Exosomes derived from oxidized LDL-stimulated macrophages attenuate the growth and tube formation of endothelial cells. Molecular Medicine Reports, 17(3), 4605–4610.PubMed

19.

Niu, C., Wang, X., Zhao, M., Cai, T., Liu, P., Li, J., et al. (2016). Macrophage foam cell-derived extracellular vesicles promote vascular smooth muscle cell migration and adhesion. Journal of the American Heart Association, 5(10).

20.

Canault, M., Leroyer, A. S., Peiretti, F., Leseche, G., Tedgui, A., Bonardo, B., et al. (2007). Microparticles of human atherosclerotic plaques enhance the shedding of the tumor necrosis factor-alpha converting enzyme/ADAM17 substrates, tumor necrosis factor and tumor necrosis factor receptor-1. The American Journal of Pathology., 171(5), 1713–1723.PubMedPubMedCentral

21.

Rautou, P. E., Leroyer, A. S., Ramkhelawon, B., Devue, C., Duflaut, D., Vion, A. C., et al. (2011). Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circulation Research, 108(3), 335–343.PubMed

22.

Fu, Z., Zhou, E., Wang, X., Tian, M., Kong, J., Li, J., et al. (2017). Oxidized low-density lipoprotein-induced microparticles promote endothelial monocyte adhesion via intercellular adhesion molecule 1. American Journal of Physiology. Cell Physiology, 313(5), C567–CC74.PubMed

23.

Hoyer, F. F., Giesen, M. K., Nunes Franca, C., Lutjohann, D., Nickenig, G., & Werner, N. (2012). Monocytic microparticles promote atherogenesis by modulating inflammatory cells in mice. Journal of Cellular and Molecular Medicine, 16(11), 2777–2788.PubMedPubMedCentral

24.

Wadey, R. M., Connolly, K. D., Mathew, D., Walters, G., Rees, D. A., & James, P. E. (2019). Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells. Atherosclerosis., 283, 19–27.PubMed

25.

Suades, R., Padro, T., Vilahur, G., & Badimon, L. (2012). Circulating and platelet-derived microparticles in human blood enhance thrombosis on atherosclerotic plaques. Thrombosis and Haemostasis, 108(6), 1208–1219.PubMed

26.

Hutcheson, J. D., Goettsch, C., Bertazzo, S., Maldonado, N., Ruiz, J. L., Goh, W., et al. (2016). Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nature Materials, 15(3), 335–343.PubMedPubMedCentral

27.

Wang, F., Chen, F. F., Shang, Y. Y., Li, Y., Wang, Z. H., Han, L., et al. (2018). Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE(-/-) mice. International Journal of Cardiology, 265, 181–187.PubMed

28.

Cai, J., Guan, W., Tan, X., Chen, C., Li, L., Wang, N., et al. (2015). SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells. Clinical Science, 129(3), 259–269.PubMed

29.

Li, C., Li, S., Zhang, F., Wu, M., Liang, H., Song, J., et al. (2018). Endothelial microparticles-mediated transfer of microRNA-19b promotes atherosclerosis via activating perivascular adipose tissue inflammation in apoE(-/-) mice. Biochemical and Biophysical Research Communications, 495(2), 1922–1929.PubMed

30.

Liu, Y., Li, Q., Hosen, M. R., Zietzer, A., Flender, A., Levermann, P., et al. (2018). Atherosclerotic conditions promote the packaging of functional microRNA-92a-3p into endothelial microvesicles. Circulation Research.

31.

Nguyen, M. A., Karunakaran, D., Geoffrion, M., Cheng, H. S., Tandoc, K., Perisic Matic, L., et al. (2018). Extracellular vesicles secreted by atherogenic macrophages transfer microRNA to inhibit cell migration. Arteriosclerosis, Thrombosis, and Vascular Biology, 1524–4636 (Electronic).

32.

Chen, L., Yang, W., Guo, Y., Chen, W., Zheng, P., Zeng, J., et al. (2017). Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis. PLoS One, 12(9), e0185406.PubMedPubMedCentral

33.

Chevillet, J. R., Kang, Q., Ruf, I. K., Briggs, H. A., Vojtech, L. N., Hughes, S. M., et al. (2014). Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proceedings of the National Academy of Sciences of the United States of America, 111(41), 14888–14893.PubMedPubMedCentral

34.

Zernecke, A., Bidzhekov, K., Noels, H., Shagdarsuren, E., Gan, L., Denecke, B., et al. (2009). Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Science Signaling, 2(100), ra81.PubMed

35.

Gu, J., Zhang, H., Ji, B., Jiang, H., Zhao, T., Jiang, R., et al. (2017). Vesicle miR-195 derived from endothelial cells inhibits expression of serotonin transporter in vessel smooth muscle cells. Scientific Reports, 7, 43546.PubMedPubMedCentral

36.

Hergenreider, E., Heydt, S., Treguer, K., Boettger, T., Horrevoets, A. J., Zeiher, A. M., et al. (2012). Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature Cell Biology, 14(3), 249–256.PubMed

37.

Huang, C., Han, J., Wu, Y., Li, S., Wang, Q., Lin, W., et al. (2018). Exosomal MALAT1 derived from oxidized low-density lipoprotein-treated endothelial cells promotes M2 macrophage polarization. Molecular Medicine Reports, 18(1), 509–515.PubMed

38.

Li, L., Wang, Z., Hu, X., Wan, T., Wu, H., Jiang, W., et al. (2016). Human aortic smooth muscle cell-derived exosomal miR-221/222 inhibits autophagy via a PTEN/Akt signaling pathway in human umbilical vein endothelial cells. Biochemical and Biophysical Research Communications, 479(2), 343–350.PubMed

39.

Li, J., Tan, M., Xiang, Q., Zhou, Z., & Yan, H. (2017). Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response. Thrombosis Research, 154, 96–105.PubMed

40.

Jansen, F., Yang, X., Proebsting, S., Hoelscher, M., Przybilla, D., Baumann, K., et al. (2014). MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. Journal of the American Heart Association, 3(6), e001249.PubMedPubMedCentral

41.

Zhu, J. J., Liu, Y. F., Zhang, Y. P., Zhao, C. R., Yao, W. J., Li, Y. S., et al. (2017). VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia. Proceedings of the National Academy of Sciences of the United States of America.

42.

Boon, R. A., & Horrevoets, A. J. (2009). Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie., 29(1), 39–40 1-3.PubMed

43.

Climent, M., Quintavalle, M., Miragoli, M., Chen, J., Condorelli, G., & Elia, L. (2015). TGFbeta triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circulation Research, 116(11), 1753–1764.PubMed

44.

Vion, A. C., Ramkhelawon, B., Loyer, X., Chironi, G., Devue, C., Loirand, G., et al. (2013). Shear stress regulates endothelial microparticle release. Circulation Research, 112(10), 1323–1333.PubMed

45.

Suades, R., Padro, T., Alonso, R., Lopez-Miranda, J., Mata, P., & Badimon, L. (2014). Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in familial hypercholesterolaemia patients. Thrombosis and Haemostasis, 111(1), 111–121.PubMed

46.

Sarlon-Bartoli, G., Bennis, Y., Lacroix, R., Piercecchi-Marti, M. D., Bartoli, M. A., Arnaud, L., et al. (2013). Plasmatic level of leukocyte-derived microparticles is associated with unstable plaque in asymptomatic patients with high-grade carotid stenosis. Journal of the American College of Cardiology, 62(16), 1436–1441.PubMed

47.

Wekesa, A. L., Cross, K. S., O'Donovan, O., Dowdall, J. F., O'Brien, O., Doyle, M., et al. (2014). Predicting carotid artery disease and plaque instability from cell-derived microparticles. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery., 48(5), 489–495.

48.

Christersson, C., Thulin, A., & Siegbahn, A. (2017). Microparticles during long-term follow-up after acute myocardial infarction. Association to atherosclerotic burden and risk of cardiovascular events. Thrombosis and Haemostasis, 117(8), 1571–1581.PubMed

49.

Sinning, J. M., Losch, J., Walenta, K., Bohm, M., Nickenig, G., & Werner, N. (2011). Circulating CD31+/annexin V+ microparticles correlate with cardiovascular outcomes. European Heart Journal, 32(16), 2034–2041.PubMed

50.

Kanhai, D. A., Visseren, F. L., van der Graaf, Y., Schoneveld, A. H., Catanzariti, L. M., Timmers, L., et al. (2013). Microvesicle protein levels are associated with increased risk for future vascular events and mortality in patients with clinically manifest vascular disease. International Journal of Cardiology, 168(3), 2358–2363.PubMed

51.

Vrijenhoek, J. E., Pasterkamp, G., Moll, F. L., de Borst, G. J., Bots, M. L., Catanzariti, L., et al. (2015). Extracellular vesicle-derived CD14 is independently associated with the extent of cardiovascular disease burden in patients with manifest vascular disease. European Journal of Preventive Cardiology, 22(4), 451–457.PubMed

52.

Eikendal, A. L., den Ruijter, H. M., Uiterwaal, C. S., Pasterkamp, G., Hoefer, I. E., de Kleijn, D. P., et al. (2014). Extracellular vesicle protein CD14 relates to common carotid intima-media thickness in eight-year-old children. Atherosclerosis., 236(2), 270–276.PubMed

53.

Finn, N. A., Eapen, D., Manocha, P., Al Kassem, H., Lassegue, B., Ghasemzadeh, N., et al. (2013). Coronary heart disease alters intercellular communication by modifying microparticle-mediated microRNA transport. FEBS Letters, 587(21), 3456–3463.PubMedPubMedCentral

54.

Miller, V. M., Lahr, B. D., Bailey, K. R., Hodis, H. N., Mulvagh, S. L., & Jayachandran, M. (2016). Specific cell-derived microvesicles: linking endothelial function to carotid artery intima-media thickness in low cardiovascular risk menopausal women. Atherosclerosis., 246, 21–28.PubMed

55.

Suades, R., Padro, T., Alonso, R., Mata, P., & Badimon, L. (2015). High levels of TSP1+/CD142+ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis. Thrombosis and Haemostasis, 114(6), 1310–1321.PubMed

56.

Chiva-Blanch, G., Padro, T., Alonso, R., Crespo, J., Perez de Isla, L., Mata, P., et al. (2019). Liquid biopsy of extracellular microvesicles maps coronary calcification and atherosclerotic plaque in asymptomatic patients with familial hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(5), 945–955.PubMed

57.

de Gonzalo-Calvo, D., Cenarro, A., Garlaschelli, K., Pellegatta, F., Vilades, D., Nasarre, L., et al. (2017). Translating the microRNA signature of microvesicles derived from human coronary artery smooth muscle cells in patients with familial hypercholesterolemia and coronary artery disease. Journal of Molecular and Cellular Cardiology, 106, 55–67.PubMed

58.

Goetzl, E. J., Schwartz, J. B., Mustapic, M., Lobach, I. V., Daneman, R., Abner, E. L., et al. (2017). Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 31(8), 3689–3694.

59.

Suades, R., Padro, T., Alonso, R., Mata, P., & Badimon, L. (2013). Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells. Thrombosis and Haemostasis, 110(2), 366–377.PubMed

60.

Wang, Z., Zhang, J., Zhang, S., Yan, S., Wang, Z., Wang, C., et al. (2019). MiR30e and miR92a are related to atherosclerosis by targeting ABCA1. Molecular Medicine Reports, 19(4), 3298–3304.PubMed

61.

Ohno, S., Drummen, G. P., & Kuroda, M. (2016). Focus on extracellular vesicles: development of extracellular vesicle-based therapeutic systems. International Journal of Molecular Sciences, 17(2), 172.PubMedPubMedCentral

62.

Alexandru, N., Andrei, E., Niculescu, L., Dragan, E., Ristoiu, V., & Georgescu, A. (2017). Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model. Acta Physiologica, 221(4), 230–249.PubMed

63.

Yi, S., Allen, S. D., Liu, Y. G., Ouyang, B. Z., Li, X., Augsornworawat, P., et al. (2016). Tailoring nanostructure morphology for enhanced targeting of dendritic cells in atherosclerosis. ACS Nano, 10(12), 11290–11303.PubMedPubMedCentral

64.

Ma, S., Tian, X. Y., Zhang, Y., Mu, C., Shen, H., Bismuth, J., et al. (2016). E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Scientific Reports, 6, 22910.PubMedPubMedCentral

65.

Elahi, F. M., Farwell, D. G., Nolta, J. A., & Anderson, J. D. (2019). Concise review: preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem cells (Dayton, Ohio).

66.

Branscome, H., Paul, S., Khatkar, P., Kim, Y., Barclay, R. A., Pinto, D. O., et al. (2019). Stem cell extracellular vesicles and their potential to contribute to the repair of damaged CNS cells. Journal of Neuroimmune Pharmacology.

67.

Vazquez-Rios, A. J., Molina-Crespo, A., Bouzo, B. L., Lopez-Lopez, R., Moreno-Bueno, G., & de la Fuente, M. (2019). Exosome-mimetic nanoplatforms for targeted cancer drug delivery. Journal of Nanobiotechnology, 17(1), 85.PubMedPubMedCentral

Title: Extracellular Vesicles as Messengers in Atherosclerosis
Authors: Mengna Peng
Xinfeng Liu
Gelin Xu
Publication date: 01-04-2020
Publisher: Springer US
Keywords: Arterial Occlusive Disease
Biomarkers
Published in: Journal of Cardiovascular Translational Research / Issue 2/2020
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-019-09923-z

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Extracellular Vesicles as Messengers in Atherosclerosis

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2020

Intermittent Occlusion of the Superior Vena Cava Reduces Cardiac Filling Pressures in Preclinical Models of Heart Failure

Heterogeneous Outcomes of Heart Failure with Better Ejection Fraction

Epicardial Application of Hydrogel with Amiodarone for Prevention of Postoperative Atrial Fibrillation in Patients After Coronary Artery Bypass Grafting

The Role of Deubiquitinases in Vascular Diseases

Effects of Adiponectin on Diastolic Function in Mice Underwent Transverse Aorta Constriction

Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page