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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Research Article

Platelet-Derived Exosomes Affect the Proliferation and Migration of Human Umbilical Vein Endothelial Cells Via miR-126

Author(s): Yan Sun, Xiao-li Liu, Dai Zhang, Fang Liu, Yu-jing Cheng, Yue Ma, Yu-jie Zhou* and Ying-xin Zhao

Volume 17, Issue 4, 2019

Page: [379 - 387] Pages: 9

DOI: 10.2174/1570161116666180313142139

Price: $65

Abstract

Background: Intraplaque angiogenesis, the process of generating new blood vessels mediated by endothelial cells, contributes to plaque growth, intraplaque hemorrhage, and thromboembolic events. Platelet-derived Exosomes (PLT-EXOs) affect angiogenesis in multiple ways. The ability of miR-126, one of the best-characterized miRNAs that regulates angiogenesis, carried by PLT-EXOs to influence angiogenesis via the regulation of the proliferation and migration of endothelial cells is unknown. In this study, we aimed to investigate the effects of PLT-EXOs on angiogenesis by Human Umbilical Vein Endothelial Cells (HUVECs).

Methods: We evaluated the levels of miR-126 and angiogenic factors in PLT-EXOs from Acute Coronary Syndrome (ACS) patients and healthy donors by real-time Polymerase Chain Reaction (PCR) and western blotting. We incubated HUVECs with PLT-EXOs and measured cell proliferation and migration with the Cell Counting Kit-8 assay and scratch assay, respectively. We also investigated the expression of miR-126 and angiogenic factors in HUVECs after exposure to PLT-EXOs by western blotting and real-time PCR.

Results: PLT-EXOs from ACS patients contained higher levels of miR-126 and angiogenic factors, including Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF), and Transforming Growth Factor Beta 1 (TGF-β1), than those from healthy donors (p<0.05). Moreover, the levels of exosomal miR-126 and angiogenic factors were increased after stimulation with thrombin (p<0.01). HUVEC proliferation and migration were promoted by treatment with activated PLT-EXOs (p<0.01); they were accompanied by the over-expression of miR-126 and angiogenic factors, including VEGF, bFGF, and TGF-β1 (p<0.01).

Conclusion: Activated PLT-EXOs promoted the proliferation and migration of HUVECs, and the overexpression of miR-126 and angiogenic factors, thereby elucidating potential new therapeutic targets for intraplaque angiogenesis.

Keywords: Intraplaque angiogenesis, platelet-derived exosomes, miR-126, human umbilical vein endothelial cells, miRNAs, inflammation, IPH.

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Graphical Abstract

[1]
Moreno PR, Purushothaman KR, Zias E, Sanz J, Fuster V. Neovascularization in human atherosclerosis. Curr Mol Med 2006; 6: 457-77.
[2]
Parma L, Baganha F, Quax PHA, Vries MRD. Plaque angiogenesis and intraplaque hemorrhage in atherosclerosis. Eur J Pharmacol 2017; 816: 107-15.
[3]
Camaré C, Pucelle M, Nègresalvayre A, Salvayre R. Angiogenesis in the atherosclerotic plaque. Redox Biol 2017; 12: 18-34.
[4]
Taruya A, Tanaka A, Nishiguchi T, et al. Vasa vasorum restructuring in human atherosclerotic plaque vulnerability: A clinical optical coherence tomography study. J Am Coll Cardiol 2015; 65: 2469-77.
[5]
Lamalice L, Boeuf FL, Huot J. Endothelial cell migration during angiogenesis. Circ Res 2007; 100: 782-94.
[6]
Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-7.
[7]
Mathivanan S, Hong J, Simpson RJ. Exosomes: Extracellular organelles important in intercellular communication. J Proteomics 2010; 73: 1907-20.
[8]
Huber HJ, Holvoet P. Exosomes: Emerging roles in communication between blood cells and vascular tissues during atherosclerosis. Curr Opin Lipidol 2015; 26: 412-9.
[9]
Lawson C, Vicencio JM, Yellon DM, Davidson SM. Microvesicles and exosomes: New players in metabolic and cardiovascular disease. J Endocrinol 2016; 228: 57-71.
[10]
Philipp VH, Schmitt MMN. Platelets and their chemokines in atherosclerosis-clinical applications. Front Physiol 2014; 5: 294.
[11]
Rautou PE, Vion AC, Amabile N, et al. Microparticles, vascular function, and atherothrombosis. Circ Res 2011; 109: 593-606.
[12]
Lukasik M, Rozalski M, Luzak B, et al. Enhanced platelet-derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients. Platelets 2013; 24: 63-70.
[13]
Torreggiani E, Perut F, Roncuzzi L, Zini N, Baglìo SR, Baldini N. Exosomes: Novel effectors of human platelet lysate activity. Eur Cell Mater 2014; 28: 137-51.
[14]
Guo SC, Tao SC, Yin WJ, Qi X, Yuan T, Zhang CQ. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics 2017; 7: 81-96.
[15]
Suárez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis. Circ Res 2009; 104: 442-54.
[16]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009; 136: 215-33.
[17]
Hu G, Drescher KM, Chen XM. Exosomal miRNAs: Biological properties and therapeutic potential. Front Genet 2012; 3: 56.
[18]
Dempsey E, Dervin F, Maguire PB. Platelet derived exosomes are enriched for specific microRNAs which regulate WNT signalling in endothelial cells. Paper presented at: The American Society of Hematology Meeting 2014.
[19]
Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 2008; 15: 272-84.
[20]
Chen JJ, Zhou SH. Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway. Cardiol J 2011; 18: 675-81.
[21]
Liang CC, Park AY, Guan JL. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2007; 2: 329-33.
[22]
Sun Y, Peng PA, Ma Y, et al. Valsartan protects against contrast-induced acute kidney injury in rats by inhibiting endoplasmic reticulum stress-induced apoptosis. Curr Vasc Pharmacol 2017; 15: 174-83.
[23]
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317-25.
[24]
Hellings WE, Peeters W, Moll FL, et al. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome a prognostic study. Circulation 2010; 121: 1941-50.
[25]
Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012; 1820: 940-8.
[26]
Chiara C, Stefania R, Antonio C, Francesco C, Giacomo DL, Riccardo A. Exosomes as intercellular signaling organelles involved in health and disease: Basic science and clinical applications. Int J Mol Sci 2013; 14: 5338-66.
[27]
Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev 2013; 32: 623-42.
[28]
Gangoda L, Boukouris S, Liem M, Kalra H, Mathivanan S. Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic? Proteomics 2015; 15: 260-71.
[29]
Hood JL, Pan H, Lanza GM, Wickline SA. Paracrine induction of endothelium by tumor exosomes. Lab Invest 2009; 89: 1317-28.
[30]
Perrotta I, Aquila S. Exosomes in human atherosclerosis: An ultrastructural analysis study. Ultrastruct Pathol 2016; 40: 101-6.
[31]
Danielson KM, Das S. Extracellular vesicles in heart disease: Excitement for the future? Exosomes Microvesicles 2014; 2
[http://dx.doi.org/10.5772/58390]
[32]
Yuan T, Guo SC, Han P, Zhang CQ, Zeng BF. Applications of leukocyte- and platelet-rich plasma (L-PRP) in trauma surgery. Curr Pharm Biotechnol 2012; 13: 1173-84.
[33]
Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: Microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and α-granules. Blood 1999; 94: 3791-9.
[34]
Wang H, Wang ZH, Kong J, et al. Oxidized low-density lipoprotein-dependent platelet-derived microvesicles trigger procoagulant effects and amplify oxidative stress. Mol Med 2012; 18: 159-66.
[35]
Barry OP, Praticò D, Savani RC, Fitzgerald GA. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998; 102: 136-44.
[36]
Srikanthan S, Li W, Silverstein RL, Mcintyre TM. Exosome poly-ubiquitin inhibits platelet activation, downregulates CD36, and inhibits pro-atherothombotic cellular functions. J Thromb Haemost 2014; 12: 1906-17.
[37]
Janiszewski M, Do Carmo AO, Pedro MA, Silva E, Knobel E, Laurindo FR. Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway. Crit Care Med 2004; 32: 818-25.
[38]
Helena GM, Alipio DODC, Luciana M, Sidney VF, Rossetti LL, Mariano J. Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: Experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care 2007; 11: 107.
[39]
Gallo A, Tandon M, Alevizos I, Illei GG. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 2012; 7: e30679.
[40]
Zhang J, Li S, Li L, et al. Exosome and exosomal microRNA: Trafficking, sorting, and function. Genomics Proteomics Bioinformatics 2015; 13: 17-24.
[41]
van Balkom BW, de Jong OG, Smits M, et al. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood 2013; 121: 3997-4006.
[42]
Liu B, Peng XC, Zheng XL, Wang J, Qin YW. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 2009; 66: 169-75.
[43]
Ueki K, Fruman DA, Yballe CM, et al. Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J Biol Chem 2003; 278: 48453-66.
[44]
Wakioka T, Sasaki A, Kato R, et al. Spred is a Sprouty-related suppressor of Ras signalling. Nature 2001; 412: 647-51.
[45]
Patrono C. Aspirin as an antiplatelet drug. N Engl J Med 1994; 330: 1287-94.
[46]
Goetzl EJ, Goetzl L, Karliner JS, Tang N, Pulliam L. Human plasma platelet-derived exosomes: Effects of aspirin. FASEB J 2016; 30: 2058-63.
[47]
de Boer HC, Van SC, Prins J, et al. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J 2013; 34: 3451-7.

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