Skip to main content

Advertisement

Log in

Impact of extracellular RNA on endothelial barrier function

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Different types of high and low molecular weight extracellular RNA (eRNA) are liberated from cells upon conditions of tissue damage or vascular diseases and have been demonstrated in vivo and in vitro to influence the integrity and barrier function of the vascular endothelium. Among the types of self eRNA studied in this respect, ribosomal RNA appears to engage cytokines to promote hyperpermeability, while counteracting RNase1 serves as a potent vessel-protective factor. Different microRNAs may change the expression program of endothelial cells with consequences for cellular contacts and stability. Non-self viral RNAs are recognized by Toll-like receptors that transmit intracellular inflammation signals to disturb the vascular barrier function, largely in connection with infectious diseases. Although derived from the same nucleotide building blocks, the various forms of eRNA exhibit a multitude of molecular interactions with the endothelium that may drastically change its phenotypical characteristics. The impact of eRNA on vascular integrity in health and disease is summarized in this concise review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

eDNA:

Extracellular DNA

eRNA:

Extracellular RNA

IL-6:

Interleukin 6

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

References

  • Abbott NJ (2000) Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol 20:131–147

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  PubMed  CAS  Google Scholar 

  • Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature 413:732–738

    Article  PubMed  CAS  Google Scholar 

  • Bálint Z, Zabini D, Konya V, Nagaraj C, Végh AG, Váró G, Wilhelm I, Fazakas C, Krizbai IA, Heinemann A, Olschewski H, Olschewski A (2013) Double-stranded RNA attenuates the barrier function of human pulmonary artery endothelial cells. PLoS ONE 8:e63776

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2009) Target recognition and regulatory functions. Cell 136:215–233

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bartel DP (2011) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Beynon HL, Haskard DO, Davies KA, Haroutunian R, Walport MJ (1993) Combinations of low concentrations of cytokines and acute agonists synergize in increasing the permeability of endothelial monolayers. Clin Exp Immunol 91:314–319

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Blobel CP (2005) ADAMS: key components in EGFR signaling and development. Nat Rev Mol Cell Biol 6:32–43

    Article  PubMed  CAS  Google Scholar 

  • Boon RA, Vickers KC (2013) Intercellular transport of microRNAs. Arterioscler Thromb Vasc Biol 33:186–192

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535

    Article  PubMed  CAS  Google Scholar 

  • Busse PJ, Buckland MS (2013) Non-histaminergic angioedema: focus on bradykinin-mediated angioedema. Clin Exp Allergy 43:385–394

    Article  PubMed  CAS  Google Scholar 

  • Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J, Arnold B, Preissner KT (2003) The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198:1507–1515

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • de Vries HE, Blom-Roosemalen MCM, van Oosten M, de Boer AG, van Berkel TJC, Breimer DD, Kuiper J (1996) The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 64:37–43

    Article  PubMed  Google Scholar 

  • Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531

    Article  PubMed  CAS  Google Scholar 

  • Dinger ME, Mercer TR, Mattick JS (2008) RNAs as extracellular signaling molecules. J Mol Endocrinol 40:151–159

    Article  PubMed  CAS  Google Scholar 

  • Duxbury MS, Ashley SW, Whang EE (2005) RNA interference: a mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells. Biochem Biophys Res Commun 331:459–463

    Article  PubMed  CAS  Google Scholar 

  • Ekström K, Valadi H, Sjöstrand M, Malmhäll C, Bossios A, Eldh M, Lötvall J (2012) Characterization of mRNA and microRNA in human mast cell-derived exosomes and their transfer to other mast cells and blood CD34 progenitor cells. J Extracell Vesicles 1:1–12

    Article  CAS  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Article  PubMed  CAS  Google Scholar 

  • Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13:34–45

    Article  PubMed  CAS  Google Scholar 

  • Fabbri M (2012) TLRs as miRNA receptors. Cancer Res 72:6333–6337

    Article  PubMed  CAS  Google Scholar 

  • Fabbri M, Paone A, Calore F, Galli R, Croce CM (2013) A new role for micro RNAs, as ligands of Toll-like receptors. RNA Biol 10:169–174

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Feinberg EH, Hunter CP (2003) Transport of ds RNA into cells by the transmembrane protein SID-1. Science 301:1545–1547

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Preissner KT (2013) Extracellular nucleic acids as novel alarm signals in the vascular system: mediators of defence and disease. Hamostaseologie 33:37–42

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Gerriets T, Wessels C, Walberer M, Kostin S, Stolz E, Zheleva K, Hocke A, Hippenstiel S, Preissner KT (2007) Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor. Blood 110:2457–2465

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Nishio M, Peters SC, Tschernatsch M, Walberer M, Weidemann S, Heidenreich R, Couraud PO, Weksler BB, Romero IA, Gerriets T, Preissner KT (2009) Signaling mechanism of extracellular RNA in endothelial cells. FASEB J 23:2100–2109

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Nishio M, Dadkhahi S, Gansler J, Saffarzadeh M, Shibamiyama A, Kral N, Baal N, Koyama T, Deindl E, Preissner KT (2011) Expression and localisation of vascular ribonucleases in endothelial cells. Thromb Haemost 105:345–355

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Grantzow T, Pagel J-I, Tschernatsch M, Sperandio M, Preissner KT, Deindl E (2012) Extracellular RNA promotes leukocyte recruitment in the vascular system by mobilizing proinflammatory cytokines. Thromb Haemost 108:730–741

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Gesierich S, Griemert B, Schänzer A, Acker T, Augustin HG, Olsson A-K, Preissner KT (2013) Extracellular RNA liberates Tumor-Necrosis-Factor-α to promote tumor cell trafficking and progression. Cancer Res 73:5080–5089

    Article  PubMed  CAS  Google Scholar 

  • Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M (2009) Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206:1983–1994

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gantier MP, Tong S, Behlke MA, Xu D, Phipps S, Foster PS, Williams BRG (2008) TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. J Immunol 180:2117–2124

    Article  PubMed  CAS  Google Scholar 

  • Gaur D, Swaminathan S, Batra JK (2001) Interaction of human pancreatic ribonuclease with human ribonuclease inhibitor: generation of inhibitor-resistant cytotoxic variants. J Biol Chem 276:24978–24984

    Article  PubMed  CAS  Google Scholar 

  • Golias C, Charalabopoulos A, Stagikas D, Charalabopoulos K, Batistatou A (2007) The kinin system-bradykinin: biological effects and clinical implications. Multiple role of the kinin system-bradykinin. Hippokratia 11:124–128

    PubMed Central  PubMed  Google Scholar 

  • Harborth J, Elbashir SM, Vandenburgh K, Manninga H, Scaringe SA, Weber K, Tuschl T (2003) Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev 13:83–105

    Article  PubMed  CAS  Google Scholar 

  • Hilton C, Karpe F (2013) Circulating microRNAs: what is their relevance? Clin Chem 59:729–731

    Article  PubMed  CAS  Google Scholar 

  • Hunter MP, Ismail N, Zhang J, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 3:e3694

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ishihara K, Kamata M, Hayashi I, Yamashina S, Majima M (2002) Roles of bradykinin in vascular permeability and angiogenesis in solid tumor. Int Immunopharmacol 2:499–509

    Article  PubMed  CAS  Google Scholar 

  • Jaax ME, Krauel K, Marschall T, Brandt S, Gansler J, Fürll B, Appel B, Fischer S, Block S, Helm CA, Müller S, Preissner KT, Greinacher A (2013) Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4. Blood 122:272–281

    Article  PubMed  CAS  Google Scholar 

  • Kannemeier C, Shibamiya A, Nakazawa F, Trusheim H, Ruppert C, Markart P, Song Y, Tzima E, Kennerknecht E, Niepmann M, von Bruehl M-L, Sedding D, Massberg S, Günther A, Engelmann B, Preissner KT (2007) Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 104:6388–6393

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kopreski MS, Benko FA, Kwak LW, Gocke CD (1999) Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin Cancer Res 5:1961–1965

    PubMed  CAS  Google Scholar 

  • Kopreski MS, Benko FA, Gocke CD (2001) Circulating RNA as a tumor marker: detection of 5T4 mRNA in breast and lung cancer patient serum. Ann NY Acad Sci 945:172–178

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM (2004) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:88–95

    Google Scholar 

  • Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858

    Article  PubMed  CAS  Google Scholar 

  • Landré JBP, Hewett PW, Olivot J-M, Friedl PYL, Sachinidis A, Moenner M (2002) Human endothelial cells selectively express large amounts of pancreatic-type ribonuclease (RNase 1). J Cell Biochem 86:540–552

    Article  PubMed  CAS  Google Scholar 

  • Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115:97–100

    Article  Google Scholar 

  • Lundberg AM, Drexler SK, Monaco C, Williams LM, Sacre SM (2007) Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood 110:3245–3252

    Article  PubMed  CAS  Google Scholar 

  • Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM (2004) TNF-α-induced increase in intestinal epithelial tight junction permeability requires NF-κB activation. Am J Physiol Gas Liv Pha 286:G367–G376

    CAS  Google Scholar 

  • Mandel P, Metais P (1947) Les acides nucleíques du plasma sangiun chez l'homme. CR Acad Sci 112:16

    Google Scholar 

  • Marcus BC, Wyble CW, Hyner KL, Gewertz BL (1996) Cytokine-induced increases in endothelial permeability occur after adhesion molecule expression. Surgery 120:411–416

    Article  PubMed  CAS  Google Scholar 

  • Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosmann C, Brinkmann V, Lorenz M, Bidzhekov K, Khandagale AB, Konrad I, Kennerknecht E, Reges K, Holdenrieder S, Braun S, Reinhardt C, Spannagl M, Preissner KT, Engelmann B (2010) Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 16:887–896

    Article  PubMed  CAS  Google Scholar 

  • Matsushima H, Yamada N, Matsue H, Shimada S (2004) TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol 173:531–541

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2001) Toll like receptors and innate immunity. Nat Rev Immunol 1:135–145

    Article  PubMed  CAS  Google Scholar 

  • Moenner M, Hatzi E, Bader J (1997) Secretion of ribonucleases by normal and immortalized cells grown in serum-free culture conditions. In Vitro Cell Dev Biol Anim 33:553–561

    Article  PubMed  CAS  Google Scholar 

  • Muhl L, Galuska SP, OÖrni K, Hernandes-Ruiz L, Andrei-Selmer LC, Geyer R, Preissner KT, Ruiz FA, Kovanen PT, Kanse SM (2009) High negative charge-to-size ratio in polyphosphates and heparin regulates factor VII-acitvating protease. FEBS J 276:4828–4839

    Article  PubMed  CAS  Google Scholar 

  • Müller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, Schmidbauer S, Gahl WA, Morrissey JH, Renne T (2009) Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139:1143–1156

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nakazawa F, Kannemeier C, Shibamiya A, Song Y, Tzima E, Schubert U, Koyama T, Niepmann M, Trusheim H, Engelmann B, Preissner KT (2005) Extracellular RNA is a natural cofacotr for the (auto-)activation of Factor VII-activating protease (FSAP). Biochem J 385:831–838

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Qureshi ST, Medzhitov R (2003) Toll-like receptors and their role in experimental models of microbial infection. Genes Immun 4:87–94

    Article  PubMed  CAS  Google Scholar 

  • Raleigh DR, Boe DM, Yu D, Weber CR, Marchiando AM, Bradford EM, Wang Y, Wu L, Schneeberger EE, Shen L, Turner JR (2011) Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function. J Cell Biol 193:565–582

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Randriamboavonjy V, Fleming I (2012) Platelet function and signaling in diabetes mellitus. Curr Vasc Pharmacol 10:532–538

    Article  PubMed  CAS  Google Scholar 

  • Reich CF, Pisetsky DS (2009) The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosis. Exp Cell Res 315:760–768

    Article  PubMed  CAS  Google Scholar 

  • Reijerkerk A, Lopez-Ramirez MA, van Het Hof B, Drexhage JA, Kamphuis WW, Kooij G, Vos JB, van der Pouw Draan TC, van Zonneveld AJ, Horrevoets AJ, Prat A, Romero IA, de Vries HE (2013) MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis. J Neurosci 33:6857–6863

    Article  PubMed  CAS  Google Scholar 

  • Römisch J, Feussner A, Vermöhlen S, Stöhr H-A (1999) The FVII activating protease cleaves single-chain plasminogen activators. Haemostasis 29:292–299

    PubMed  Google Scholar 

  • Rose-John S (2013) ADAM17, shedding, TACE as therapeutic targets. Pharmacol Res 71:19–22

    Article  PubMed  CAS  Google Scholar 

  • Rosi A, Guidoni L, Luciani AM, Mariutti G, Viti V (1988) RNA-lipid complexes released from the plasma emembrane of human colon carcinoma cells. Cancer Lett 39:153–160

    Article  PubMed  CAS  Google Scholar 

  • Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KT (2012) Neutrophil extracellular traps directly induce epithelial and endothelial death: a predominant role of histones. PLoS ONE 7:e32366

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Schmaier AH (2008) Assembly, activation, and physiologic influence of the plasma kallikrein/kinin system. Int Immunopharmacol 8:161–165

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sedgwick JB, Menon I, Gern JE, Busse WW (2002) Effects of inflammatory cytokines on the permeability of human lung microvascular endothelial cell monolayers and differential eosinophil transmigration. J Allergy Clin Immunol 110:752–756

    Article  PubMed  CAS  Google Scholar 

  • Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S, Konstin S, Baumer Y, Liehn EA, Weber C, Boisvert WA, Preissner KT, Zernecke A (2014) The role of extracellular RNA in atherosclerotic plaque formation in mice. Circulation 129:598–606

    Article  PubMed  CAS  Google Scholar 

  • Sirois CM, Jin T, Miller AL, Bertheloot D, Nakamura H, Horvath GL, Mian A, Jiang J, Schrum J, Bossaller L, Pelka K, Garbi N, Brewah Y, Tian J, Chang C, Chowdhury PS, Sims GP, Kolbeck R, Coyle AJ, Humbles AA, Xiao TS, Latz E (2013) RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA. J Exp Med 210:2447–2463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sisco KL (2000) Is RNA in serum bound to nucleoprotein complexes? Clin Chem 47:1744–1745

    Google Scholar 

  • Staddon JM, Herrenknecht K, Smales C, Rubin LL (1995) Evidence that tyrosine phosphorylation may increase tight junction permeability. J Cell Sci 108:609–619

    PubMed  CAS  Google Scholar 

  • Stroun M, Anker P, Beljanski M, Henri J, Lederrey C, Ojha M (1978) Presence of RNA in the nucleoprotein complex spontaneously released by human lymphocytes and frog auricles in culture. Cancer Res 38:3546–3554

    PubMed  CAS  Google Scholar 

  • Stutz A, Bertheloot D, Latz E (2011) Innate immune receptors for nucleic acids. Methods Mol Biol 748:69–82

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Yoshinaga N, Tanabe S (2011) IL-6 regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem 286:31263–31271

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tan EM, Schur PH, Carr RI, Kunkel HG (1966) Deoxybonucleic (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest 45:1732–1740

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Taylor LT, Wahl-Jensen V, Copeland AM, Jahrling PB, Schmaljohn CS (2013) Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system. PLos Pathogens 9:e1003470

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Urbich C, Kuehbacher A, Dimmeler S (2008) Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 79:581–588

    Article  PubMed  CAS  Google Scholar 

  • Valiunas V, Polosina YY, Miller H, Ppotapova IA, Valiuniene L, Doronin S, Mathias RT, Robinson RB, Rosen MR, Cohen IS, Brink PR (2005) Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. J Physiol 568:459–468

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • van der Meijden PEJ, Heemskerk JWM (2010) Polyphosphates: a link between platelet activation, intrinsic coagulation and inflammation? Expert Rev Hematol 3:269–272

    Article  PubMed  Google Scholar 

  • van Nieuw Amerongen GP, Beckers CM, Achekar ID, Zeeman S, Musters RJ, Hinsbergh VW (2007) Involvement of Rho kinase in endothelial barrier maintenance. Arterioscler Thromb Vasc Biol 27:2332–2339

    Article  PubMed  CAS  Google Scholar 

  • von Brühl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Köllnberger M, Byrne RA, Laitinen I, Walch A, Brill A, Pfeifer S, Manukyan D, Braun S, Lange P, Riegger J, Ware J, Eckart A, Haidari S, Rudelius M, Schulz C, Echtler K, Brinkmann V, Schwaiger M, Preissner KT, Sagner DD, Mackman N, Engelmann B, Massberg S (2012) Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 209:819–835

    Article  CAS  Google Scholar 

  • Walberer M, Tschernatsch M, Fischer S, Ritschel N, Volk K, Friedrich C, Bachmann G, Mueller C, Kaps M, Nedelmann M, Blaes F, Preissner KT, Gerriets T (2009) RNase therapy assessed by magnetic resonance imaging reduces cerebral edema and infarction size in acute stroke. Curr Neurovasc Res 6:12–19

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA (2004) Toll-like receptor 3 mediates west nile virus entry into the brain causing lethal encephalitis. Nat Med 12:1366–1373

    Article  CAS  Google Scholar 

  • Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN (2008) The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wieczorek AJ, Rhyner C, Block LH (1985) Isolation and characterization of an RNA-proteolipid complex assiciated with the malignant state in humans. Proc Natl Acad Sci USA 82:3455–3459

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Winston WM, Molodowitch C, Hunter CP (2002) Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295:2456–2459

    Article  PubMed  CAS  Google Scholar 

  • Xiao T (2009) Innate immune recognition of nucleic acids. Immunol Res 43:98–108

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the experimental work of Dr. Mohammad Aslam (Dept. Physiology, JLU Giessen). The work of the authors cited in this article was supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn (Germany) (Excellence Cluster “Cardiopulmonary System”, ECCPS; grants FI 543/2-1 and IRTG-1566).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Klaus T. Preissner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fischer, S., Cabrera-Fuentes, H.A., Noll, T. et al. Impact of extracellular RNA on endothelial barrier function. Cell Tissue Res 355, 635–645 (2014). https://doi.org/10.1007/s00441-014-1850-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1850-8

Keywords

Navigation