Semin Thromb Hemost 2018; 44(03): 216-223
DOI: 10.1055/s-0037-1612623
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Evolving Role of MicroRNAs in Endothelial Cell Dysfunction in Response to Infection

Rebecca L. Watkin
1   Cardiovascular Infection Research Group, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Glenn G. Fitzpatrick
1   Cardiovascular Infection Research Group, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Steve W. Kerrigan
1   Cardiovascular Infection Research Group, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 January 2018 (online)

Abstract

The microRNAs are short noncoding RNA molecules responsible for translational repression and silencing of target genes via binding to the mRNA. They are found in all eukaryotic cells and play a critical role in virtually all physiological processes, including within the cardiovascular system where they influence cellular development, differentiation, cardiovascular function, hemostasis, and programmed cell death. Dysregulated microRNA expression is associated with several conditions ranging from cancer and autoimmune disease to infection. Progressively, it has become increasingly clear that microRNAs are important components of the host response to microbes. The cardiovascular system, coupled with cells of the innate immune system, provide the initial interaction and first response to microbial infection, respectively. This review presents the current state of knowledge regarding the role of microRNAs with emphasis on their role in controlling endothelial cell function.

 
  • References

  • 1 Sumpio BE, Riley JT, Dardik A. Cells in focus: endothelial cell. Int J Biochem Cell Biol 2002; 34 (12) 1508-1512
  • 2 Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010; 4: 302-312
  • 3 Jacob M, Chappell D, Becker BF. Regulation of blood flow and volume exchange across the microcirculation. Crit Care 2016; 20 (01) 319
  • 4 Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 2004; 84 (03) 869-901
  • 5 Berg JM, Tymoczko JL, Stryer L. Biochemistry, 5th ed. New York, NY: W. H. Freeman; 2002
  • 6 Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function, and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778 (03) 660-669
  • 7 Günzel D, Yu AS. Claudins and the modulation of tight junction permeability. Physiol Rev 2013; 93 (02) 525-569
  • 8 Granger DN, Kubes P. The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 1994; 55 (05) 662-675
  • 9 Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord 2015; 15: 130
  • 10 Dole VS, Bergmeier W, Mitchell HA, Eichenberger SC, Wagner DD. Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin. Blood 2005; 106 (07) 2334-2339
  • 11 Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ. The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor. Blood 1995; 85 (11) 3150-3157
  • 12 Overbey DM, Jones EL, Robinson TN. How hemostatic agents interact with the coagulation cascade. AORN J 2014; 100 (02) 148-159
  • 13 Denis C, Methia N, Frenette PS. , et al. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci U S A 1998; 95 (16) 9524-9529
  • 14 Davis SF, Yeung AC, Meredith IT. , et al. Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant. Circulation 1996; 93 (03) 457-462
  • 15 MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964; 202: 498-499
  • 16 Chu AJ. Tissue factor, blood coagulation, and beyond: an overview. Int J Inflamm 2011; 2011: 367284
  • 17 Cugno M, Cicardi M, Bottasso B. , et al. Activation of the coagulation cascade in C1-inhibitor deficiencies. Blood 1997; 89 (09) 3213-3218
  • 18 Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 1991; 30 (43) 10363-10370
  • 19 Rajendran P, Rengarajan T, Thangavel J. , et al. The vascular endothelium and human diseases. Int J Biol Sci 2013; 9 (10) 1057-1069
  • 20 Rask-Madsen C, Li Q, Freund B. , et al. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell Metab 2010; 11 (05) 379-389
  • 21 Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 2009; 1 (04) a000034
  • 22 Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci 2016; 17 (10) E1712
  • 23 Obernosterer G, Leuschner PJ, Alenius M, Martinez J. Post-transcriptional regulation of microRNA expression. RNA 2006; 12 (07) 1161-1167
  • 24 Ekimler S, Sahin K. Computational methods for microRNA target prediction. Genes (Basel) 2014; 5 (03) 671-683
  • 25 Oler AJ, Alla RK, Roberts DN. , et al. Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat Struct Mol Biol 2010; 17 (05) 620-628
  • 26 Lee Y, Kim M, Han J. , et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004; 23 (20) 4051-4060
  • 27 Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006; 13 (12) 1097-1101
  • 28 Lee Y, Ahn C, Han J. , et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425 (6956): 415-419
  • 29 Westholm JO, Lai EC. Mirtrons: microRNA biogenesis via splicing. Biochimie 2011; 93 (11) 1897-1904
  • 30 Havens MA, Reich AA, Duelli DM, Hastings ML. Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic Acids Res 2012; 40 (10) 4626-4640
  • 31 Köhler A, Hurt E. Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol 2007; 8 (10) 761-773
  • 32 Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004; 10 (02) 185-191
  • 33 Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136 (02) 215-233
  • 34 Macfarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer. Curr Genomics 2010; 11 (07) 537-561
  • 35 Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15 (08) 509-524
  • 36 Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009; 11 (03) 228-234
  • 37 Cantini L, Isella C, Petti C. , et al. MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes. Nat Commun 2015; 6: 8878
  • 38 Khorshid M, Hausser J, Zavolan M, van Nimwegen E. A biophysical miRNA-mRNA interaction model infers canonical and noncanonical targets. Nat Methods 2013; 10 (03) 253-255
  • 39 Andrés-León E, Cases I, Alonso S, Rojas AM. Novel miRNA-mRNA interactions conserved in essential cancer pathways. Sci Rep 2017; 7: 46101
  • 40 Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 2012; 13 (04) 271-282
  • 41 Thomson DW, Bracken CP, Goodall GJ. Experimental strategies for microRNA target identification. Nucleic Acids Res 2011; 39 (16) 6845-6853
  • 42 Suárez Y, Fernández-Hernando C, Yu J. , et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci U S A 2008; 105 (37) 14082-14087
  • 43 Wronska A, Kurkowska-Jastrzebska I, Santulli G. Application of microRNAs in diagnosis and treatment of cardiovascular disease. Acta Physiol (Oxf) 2015; 213 (01) 60-83
  • 44 Wang S, Aurora AB, Johnson BA. , et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 2008; 15 (02) 261-271
  • 45 Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A 2008; 105 (05) 1516-1521
  • 46 Liu X, Cheng Y, Yang J, Xu L, Zhang C. Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application. J Mol Cell Cardiol 2012; 52 (01) 245-255
  • 47 Weber M, Baker MB, Moore JP, Searles CD. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun 2010; 393 (04) 643-648
  • 48 Ji R, Cheng Y, Yue J. , et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 2007; 100 (11) 1579-1588
  • 49 Sabatel C, Malvaux L, Bovy N. , et al. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells. PLoS One 2011; 6 (02) e16979
  • 50 Aksu K, Donmez A, Keser G. Inflammation-induced thrombosis: mechanisms, disease associations and management. Curr Pharm Des 2012; 18 (11) 1478-1493
  • 51 Cheng HS, Sivachandran N, Lau A. , et al. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med 2013; 5 (07) 1017-1034
  • 52 Roos J, Enlund E, Funcke JB. , et al. miR-146a-mediated suppression of the inflammatory response in human adipocytes. Sci Rep 2016; 6: 38339
  • 53 Wang JF, Yu ML, Yu G. , et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun 2010; 394 (01) 184-188
  • 54 Sun X, Icli B, Wara AK. , et al; MICU Registry. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Invest 2012; 122 (06) 1973-1990
  • 55 Suárez Y, Wang C, Manes TD, Pober JS. Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J Immunol 2010; 184 (01) 21-25
  • 56 Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A 2010; 107 (30) 13450-13455
  • 57 Vasa-Nicotera M, Chen H, Tucci P. , et al. miR-146a is modulated in human endothelial cell with aging. Atherosclerosis 2011; 217 (02) 326-330
  • 58 Olivieri F, Lazzarini R, Recchioni R. , et al. MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling. Age (Dordr) 2013; 35 (04) 1157-1172
  • 59 Cichon C, Sabharwal H, Rüter C, Schmidt MA. MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions. Tissue Barriers 2014; 2 (04) e944446
  • 60 Zhuang Y, Peng H, Mastej V, Chen W. MicroRNA Regulation of Endothelial Junction Proteins and Clinical Consequence. Mediators Inflamm 2016; 2016: 5078627
  • 61 Rajput C, Tauseef M, Farazuddin M. , et al. MicroRNA-150 suppression of angiopoetin-2 generation and signaling is crucial for resolving vascular injury. Arterioscler Thromb Vasc Biol 2016; 36 (02) 380-388
  • 62 Fang Z, He QW, Li Q. , et al. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. FASEB J 2016; 30 (06) 2097-2107
  • 63 Hu D, Yu Y, Wang C, Li D, Tai Y, Fang L. microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1. Eur J Med Res 2015; 20: 51
  • 64 Miao YS, Zhao YY, Zhao LN. , et al. MiR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of ZO-1, occludin and claudin-5. Cell Signal 2015; 27 (01) 156-167
  • 65 Zhou W, Fong MY, Min Y. , et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014; 25 (04) 501-515
  • 66 Ambros V. MicroRNAs: genetically sensitized worms reveal new secrets. Curr Biol 2010; 20 (14) R598-R600
  • 67 Wang JW, Valentijn JA, Valentijn KM. , et al. Formation of platelet-binding von Willebrand factor strings on non-endothelial cells. J Thromb Haemost 2012; 10 (10) 2168-2178
  • 68 Ikezoe T. Thrombomodulin/activated protein C system in septic disseminated intravascular coagulation. J Intensive Care 2015; 3 (01) 1
  • 69 Østerud B, Bjørklid E. The tissue factor pathway in disseminated intravascular coagulation. Semin Thromb Hemost 2001; 27 (06) 605-617
  • 70 Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014; 64 (01) 57-80
  • 71 Sahni A, Narra HP, Patel J, Sahni SK. MicroRNA signature of human microvascular endothelium infected with Rickettsia rickettsii . Int J Mol Sci 2017; 18 (07) E1471
  • 72 Wu M, Gu JT, Yi B, Tang ZZ, Tao GC. microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis. Exp Ther Med 2015; 9 (04) 1125-1132
  • 73 Kalani M, Hodjati H, GhamarTalepoor A, Samsami Dehaghani A, Doroudchi M. CagA-positive and CagA-negative Helicobacter pylori strains differentially affect the expression of micro RNAs 21, 92a, 155 and 663 in human umbilical vein endothelial cells. Cell Mol Biol 2017; 63 (01) 34-40
  • 74 Urbich C, Kaluza D, Frömel T. , et al. MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood 2012; 119 (06) 1607-1616
  • 75 Kane NM, Howard L, Descamps B. , et al. Role of microRNAs 99b, 181a, and 181b in the differentiation of human embryonic stem cells to vascular endothelial cells. Stem Cells 2012; 30 (04) 643-654
  • 76 Ma J, Yao Y, Wang P. , et al. MiR-181a regulates blood-tumor barrier permeability by targeting Krüppel-like factor 6. J Cereb Blood Flow Metab 2014; 34 (11) 1826-1836
  • 77 Landskroner-Eiger S, Qiu C, Perrotta P. , et al. Endothelial miR-17 approximately 92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling. Proc Natl Acad Sci U S A 2015; 112 (41) 12812-12817
  • 78 Liu W, Cai H, Lin M. , et al. MicroRNA-107 prevents amyloid-beta induced blood-brain barrier disruption and endothelial cell dysfunction by targeting Endophilin-1. Exp Cell Res 2016; 343 (02) 248-257
  • 79 Li Y, Yang C, Zhang L, Yang P. MicroRNA-210 induces endothelial cell apoptosis by directly targeting PDK1 in the setting of atherosclerosis. Cell Mol Biol Lett 2017; 22: 3
  • 80 Atkin-Smith GK, Tixeira R, Paone S. , et al. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat Commun 2015; 6: 7439
  • 81 Dullea RG, Robinson JF, Bedford JS. Nonrandom degradation of DNA in human leukemic cells during radiation-induced apoptosis. Cancer Res 1999; 59 (15) 3712-3718
  • 82 Crawford S, Diamond D, Brustolon L, Penarreta R. Effect of increased extracellular ca on microvesicle production and tumor spheroid formation. Cancer Microenviron 2010; 4 (01) 93-103
  • 83 Clark MR. Flippin' lipids. Nat Immunol 2011; 12 (05) 373-375
  • 84 Devaux PF, Herrmann A, Ohlwein N, Kozlov MM. How lipid flippases can modulate membrane structure. Biochim Biophys Acta 2008; 1778 (7-8): 1591-1600
  • 85 Lenoir G, Williamson P, Holthuis JC. On the origin of lipid asymmetry: the flip side of ion transport. Curr Opin Chem Biol 2007; 11 (06) 654-661
  • 86 Contreras FX, Sánchez-Magraner L, Alonso A, Goñi FM. Transbilayer (flip-flop) lipid motion and lipid scrambling in membranes. FEBS Lett 2010; 584 (09) 1779-1786
  • 87 Vanlandingham PA, Ceresa BP. Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. J Biol Chem 2009; 284 (18) 12110-12124
  • 88 Nieuwland R, Berckmans RJ, McGregor S. , et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95 (03) 930-935
  • 89 Wang JG, Manly D, Kirchhofer D, Pawlinski R, Mackman N. Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic mice. J Thromb Haemost 2009; 7 (07) 1092-1098
  • 90 VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59 (02) 277-287
  • 91 Petrozella L, Mahendroo M, Timmons B, Roberts S, McIntire D, Alexander JM. Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period. Am J Obstet Gynecol 2012; 207 (02) 140.e20-140.e26
  • 92 Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 2006; 48 (02) 180-186
  • 93 Curtis AM, Wilkinson PF, Gui M, Gales TL, Hu E, Edelberg JM. p38 mitogen-activated protein kinase targets the production of proinflammatory endothelial microparticles. J Thromb Haemost 2009; 7 (04) 701-709
  • 94 Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro-oncol 2005; 7 (04) 452-464
  • 95 Yamamoto S, Niida S, Azuma E. , et al. Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes. Sci Rep 2015; 5: 8505
  • 96 Hergenreider E, Heydt S, Tréguer K. , et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 2012; 14 (03) 249-256
  • 97 Zhang J, Ren J, Chen H, Geng Q. Inflammation induced-endothelial cells release angiogenesis associated-microRNAs into circulation by microparticles. Chin Med J (Engl) 2014; 127 (12) 2212-2217
  • 98 Jansen F, Yang X, Baumann K. , et al. Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism. J Cell Mol Med 2015; 19 (09) 2202-2214
  • 99 Jansen F, Yang X, Hoelscher M. , et al. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation 2013; 128 (18) 2026-2038
  • 100 Njock MS, Cheng HS, Dang LT. , et al. Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing antiinflammatory microRNAs. Blood 2015; 125 (20) 3202-3212
  • 101 Brostjan C, Anrather J, Csizmadia V, Natarajan G, Winkler H. Glucocorticoids inhibit E-selectin expression by targeting NF-kappaB and not ATF/c-Jun. J Immunol 1997; 158 (08) 3836-3844
  • 102 Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest 2001; 107 (02) 135-142
  • 103 Kuhn AR, Schlauch K, Lao R, Halayko AJ, Gerthoffer WT, Singer CA. MicroRNA expression in human airway smooth muscle cells: role of miR-25 in regulation of airway smooth muscle phenotype. Am J Respir Cell Mol Biol 2010; 42 (04) 506-513
  • 104 Loyer X, Potteaux S, Vion AC. , et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res 2014; 114 (03) 434-443
  • 105 Zhang J, Li SF, Chen H, Song JX. MiR-106b-5p inhibits tumor necrosis factor-α-induced apoptosis by targeting phosphatase and tensin homolog deleted on chromosome 10 in vascular endothelial cells. Chin Med J (Engl) 2016; 129 (12) 1406-1412
  • 106 Xin M, Small EM, Sutherland LB. , et al. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev 2009; 23 (18) 2166-2178
  • 107 Chatterjee V, Beard Jr RS, Reynolds JJ. , et al. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression. PLoS One 2014; 9 (10) e110286