Semin Hear 2012; 33(03): 242-250
DOI: 10.1055/s-0032-1315723
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vascular Pathophysiology in Hearing Disorders

Dennis R. Trune
1   Department of Otolaryngology–Head & Neck Surgery, Oregon Hearing Research Center, Oregon Health & Science University, Portland, Oregon
,
Anh Nguyen-Huynh
1   Department of Otolaryngology–Head & Neck Surgery, Oregon Hearing Research Center, Oregon Health & Science University, Portland, Oregon
› Author Affiliations
Further Information

Publication History

Publication Date:
31 July 2012 (online)

Abstract

The inner ear vasculature is responsible for maintenance of the blood-labyrinth barrier, transport of systemic hormones for ion homeostasis, and supplying nutrients for metabolic functions. Unfortunately, these blood vessels also expose the ear to circulating inflammatory factors resulting from systemic diseases. Thus, although the inner ear blood vessels are critical for normal function, they also facilitate pathological mechanisms that result in hearing and vestibular dysfunction. Despite these numerous critical roles of inner ear vasculature, little is known of its normal homeostatic functions and how these are compromised in disease. The objective of this review is to discuss the current concepts of vascular biology, how blood vessels naturally respond to circulating inflammatory factors, and how such mechanisms of vascular pathophysiology may cause hearing loss.

 
  • References

  • 1 Shi X. Physiopathology of the cochlear microcirculation. Hear Res 2011; 282: 10-24
  • 2 Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 2007; 454: 345-359
  • 3 Taylor KR, Gallo RL. Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation. FASEB J 2006; 20: 9-22
  • 4 Pries AR, Kuebler WM. Normal endothelium. Handb Exp Pharmacol 2006; (176 Pt 1) 1-40
  • 5 Bernfield M, Götte M, Park PW , et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 1999; 68: 729-777
  • 6 Broekhuizen LN, Mooij HL, Kastelein JJ, Stroes ES, Vink H, Nieuwdorp M. Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease. Curr Opin Lipidol 2009; 20: 57-62
  • 7 Nieuwdorp M, Meuwese MC, Vink H, Hoekstra JB, Kastelein JJ, Stroes ES. The endothelial glycocalyx: a potential barrier between health and vascular disease. Curr Opin Lipidol 2005; 16: 507-511
  • 8 Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003; 101: 3765-3777
  • 9 Woodfin A, Voisin MB, Imhof BA, Dejana E, Engelhardt B, Nourshargh S. Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood 2009; 113: 6246-6257
  • 10 Cheng Q, McKeown SJ, Santos L , et al. Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules. J Immunol 2010; 185: 1238-1247
  • 11 Mulivor AW, Lipowsky HH. Role of glycocalyx in leukocyte-endothelial cell adhesion. Am J Physiol Heart Circ Physiol 2002; 283: H1282-H1291
  • 12 Nieuwdorp M, Meuwese MC, Mooij HL , et al. Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation. Atherosclerosis 2009; 202: 296-303
  • 13 Marcus BC, Hynes KL, Gewertz BL. Loss of endothelial barrier function requires neutrophil adhesion. Surgery 1997; 122: 420-426 ; discussion 426–427
  • 14 Iversen PO, Nicolaysen A, Kvernebo K, Benestad HB, Nicolaysen G. Human cytokines modulate arterial vascular tone via endothelial receptors. Pflugers Arch 1999; 439: 93-100
  • 15 Henry CB, Duling BR. TNF-alpha increases entry of macromolecules into luminal endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol 2000; 279: H2815-H2823
  • 16 Meroni PL, Borghi MO, Raschi E , et al. Inflammatory response and the endothelium. Thromb Res 2004; 114: 329-334
  • 17 Raschi E, Testoni C, Bosisio D , et al. Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood 2003; 101: 3495-3500
  • 18 Del Papa N, Sheng YH, Raschi E , et al. Human beta 2-glycoprotein I binds to endothelial cells through a cluster of lysine residues that are critical for anionic phospholipid binding and offers epitopes for anti-beta 2-glycoprotein I antibodies. J Immunol 1998; 160: 5572-5578
  • 19 Hamid C, Norgate K, D'Cruz DP , et al. Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome. Ann Rheum Dis 2007; 66: 1000-1007
  • 20 Pierangeli SS, Chen PP, González EB. Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol 2006; 13: 366-375
  • 21 Harel M, Aron-Maor A, Sherer Y, Blank M, Shoenfeld Y. The infectious etiology of the antiphospholipid syndrome: links between infection and autoimmunity. Immunobiology 2005; 210: 743-747
  • 22 Blank M, Asherson RA, Cervera R, Shoenfeld Y. Antiphospholipid syndrome infectious origin. J Clin Immunol 2004; 24: 12-23
  • 23 Blank M, Barzilai O, Shoenfeld Y. Molecular mimicry and auto-immunity. Clin Rev Allergy Immunol 2007; 32: 111-118
  • 24 Abi-Hachem RN, Zine A, Van De Water TR. The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Patents CNS Drug Discov 2010; 5: 147-163
  • 25 Chappell D, Hofmann-Kiefer K, Jacob M , et al. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol 2009; 104: 78-89
  • 26 Felinski EA, Antonetti DA. Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy. Curr Eye Res 2005; 30: 949-957
  • 27 Underwood JL, Murphy CG, Chen J , et al. Glucocorticoids regulate transendothelial fluid flow resistance and formation of intercellular junctions. Am J Physiol 1999; 277 (2 Pt 1) C330-C342
  • 28 Dai M, Shi X. Fibro-vascular coupling in the control of cochlear blood flow. PLoS ONE 2011; 6: e20652
  • 29 Tagaya M, Yamazaki M, Teranishi M , et al. Endolymphatic hydrops and blood-labyrinth barrier in Ménière's disease. Acta Otolaryngol 2011; 131: 474-479
  • 30 Scherer EQ, Yang J, Canis M , et al. Tumor necrosis factor-α enhances microvascular tone and reduces blood flow in the cochlea via enhanced sphingosine-1-phosphate signaling. Stroke 2010; 41: 2618-2624
  • 31 Tomoda K, Yamawaki T, Suzuka Y, Yamashita T, Kumazawa T. Alterations of charge barrier in the inner ear following immune reactions. Ann Otol Rhinol Laryngol Suppl 1992; 157: 63-66
  • 32 Torihara K, Suganuma T, Ide S, Morimitsu T. Anionic sites in blood capillaries of the mouse cochlear duct. Hear Res 1994; 77: 69-74
  • 33 Trune DR, Hausman F, Kempton B. Cochlear ion homeostasis mechanisms are suppressed in autoimmune inner ear disease and restored by glucocorticoid treatment. In: Association Research Otolaryngology (Abstract). Baltimore, MD: 2011
  • 34 Trune DR. Ion homeostasis in the ear: mechanisms, maladies, and management. Curr Opin Otolaryngol Head Neck Surg 2010; 18: 413-419
  • 35 Hilger JA. The common ground of allergy, autonomic dysfunction and endocrine imbalance. Trans Am Acad Ophthalmol Otolaryngol 1953; 57: 443-446
  • 36 Furuta T, Teranishi M, Uchida Y , et al. Association of interleukin-1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease. Int J Immunogenet 2011; 38: 249-254
  • 37 Pathak S, Goldofsky E, Vivas EX, Bonagura VR, Vambutas A. IL-1β is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J Immunol 2011; 186: 1870-1879
  • 38 Vambutas A, DeVoti J, Goldofsky E, Gordon M, Lesser M, Bonagura V. Alternate splicing of interleukin-1 receptor type II (IL1R2) in vitro correlates with clinical glucocorticoid responsiveness in patients with AIED. PLoS ONE 2009; 4: e5293
  • 39 Van Wijk F, Staecker H, Keithley E, Lefebvre PP. Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurootol 2006; 11: 357-365
  • 40 Rahman MU, Poe DS, Choi HK. Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study. Otol Neurotol 2001; 22: 619-624
  • 41 Matteson EL, Choi HK, Poe DS , et al. Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center, open-label, pilot study. Arthritis Rheum 2005; 53: 337-342
  • 42 Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol 2005; 26: 903-907
  • 43 George DL, Pradhan S. Idiopathic sensorineural hearing disorders in adults—a pragmatic approach. Nat Rev Rheumatol 2009; 5: 505-512
  • 44 Kanzaki J, Kanzaki S, Ogawa K. Long-term prognosis of steroid-dependent sensorineural hearing loss. Audiol Neurootol 2009; 14: 26-34
  • 45 Dornhoffer JL, Arenberg JG, Arenberg IK, Shambaugh Jr GE. Pathophysiological mechanisms in immune inner ear disease. Acta Otolaryngol Suppl 1997; 526: 30-36
  • 46 Amor Dorado JC, Barreira Fernández MdelP, Regueiro Villarin S, González-Gay MA. [Audiovestibular manifestations in systemic vasculitis]. Acta Otorrinolaringol Esp 2009; 60: 432-442
  • 47 Brookes GB. Circulating immune complexes in Meniere's disease. Arch Otolaryngol Head Neck Surg 1986; 112: 536-540
  • 48 Derebery MJ, Rao VS, Siglock TJ, Linthicum FH, Nelson RA. Menière's disease: an immune complex-mediated illness?. Laryngoscope 1991; 101: 225-229
  • 49 Kariya S, Cureoglu S, Fukushima H , et al. Vascular findings in the stria vascularis of patients with unilateral or bilateral Ménière's disease: a histopathologic temporal bone study. Otol Neurotol 2009; 30: 1006-1012
  • 50 Savastano M, Giacomelli L, Marioni G. Non-specific immunological determinations in Meniere's disease: any role in clinical practice?. Eur Arch Otorhinolaryngol 2007; 264: 15-19
  • 51 Psifidis AD, Psillas GK, Daniilidis JCh. Sudden sensorineural hearing loss: long-term follow-up results. Otolaryngol Head Neck Surg 2006; 134: 809-815
  • 52 Merchant SN, Durand ML, Adams JC. Sudden deafness: is it viral?. ORL J Otorhinolaryngol Relat Spec 2008; 70: 52-60 ; discussion 60–62
  • 53 Lazarini PR, Camargo AC. Idiopathic sudden sensorineural hearing loss: etiopathogenic aspects. Braz J Otorhinolaryngol 2006; 72: 554-561
  • 54 Evans KL, Baldwin DL, Bainbridge D, Morrison AW. Immune status in patients with Menière's disease. Arch Otorhinolaryngol 1988; 245: 287-292
  • 55 Brookes GB. Immune complex-associated deafness: preliminary communication. J R Soc Med 1985; 78: 47-55
  • 56 Agrup C, Luxon LM. Immune-mediated inner-ear disorders in neuro-otology. Curr Opin Neurol 2006; 19: 26-32
  • 57 Shi X. Cochlear pericyte responses to acoustic trauma and the involvement of hypoxia-inducible factor-1alpha and vascular endothelial growth factor. Am J Pathol 2009; 174: 1692-1704
  • 58 Zou J, Pyykkö I, Sutinen P, Toppila E. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF. Hear Res 2005; 202: 13-20
  • 59 Yang Y, Dai M, Wilson TM , et al. Na+/K+-ATPase α1 identified as an abundant protein in the blood-labyrinth barrier that plays an essential role in the barrier integrity. PLoS ONE 2011; 6: e16547
  • 60 Stearns GS, Keithley EM, Harris JP. Development of high endothelial venule-like characteristics in the spiral modiolar vein induced by viral labyrinthitis. Laryngoscope 1993; 103: 890-898
  • 61 Solares CA, Edling AE, Johnson JM , et al. Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. J Clin Invest 2004; 113: 1210-1217
  • 62 Lorenz RR, Solares CA, Williams P , et al. Interferon-gamma production to inner ear antigens by T cells from patients with autoimmune sensorineural hearing loss. J Neuroimmunol 2002; 130: 173-178
  • 63 Baek MJ, Park HM, Johnson JM , et al. Increased frequencies of cochlin-specific T cells in patients with autoimmune sensorineural hearing loss. J Immunol 2006; 177: 4203-4210
  • 64 Lunardi C, Bason C, Leandri M , et al. Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome. Lancet 2002; 360: 915-921
  • 65 Roverano S, Cassano G, Paira S , et al. Asymptomatic sensorineural hearing loss in patients with systemic lupus erythematosus. J Clin Rheumatol 2006; 12: 217-220
  • 66 Nacci A, Dallan I, Monzani F , et al. Elevated antithyroid peroxidase and antinuclear autoantibody titers in Ménière's disease patients: more than a chance association?. Audiol Neurootol 2010; 15: 1-6
  • 67 Mathews J, Kumar BN. Autoimmune sensorineural hearing loss. Clin Otolaryngol Allied Sci 2003; 28: 479-488
  • 68 Kastanioudakis I, Ziavra N, Voulgari PV, Exarchakos G, Skevas A, Drosos AA. Ear involvement in systemic lupus erythematosus patients: a comparative study. J Laryngol Otol 2002; 116: 103-107
  • 69 Berrocal JR, Ramírez-Camacho R. Sudden sensorineural hearing loss: supporting the immunologic theory. Ann Otol Rhinol Laryngol 2002; 111: 989-997
  • 70 Cadoni G, Fetoni AR, Agostino S , et al. Autoimmunity in sudden sensorineural hearing loss: possible role of anti-endothelial cell autoantibodies. Acta Otolaryngol Suppl 2002; (548) 30-33
  • 71 Ottaviani F, Cadoni G, Marinelli L , et al. Anti-endothelial autoantibodies in patients with sudden hearing loss. Laryngoscope 1999; 109 (7 Pt 1) 1084-1087
  • 72 Mouadeb DA, Ruckenstein MJ. Antiphospholipid inner ear syndrome. Laryngoscope 2005; 115: 879-883
  • 73 Yehudai D, Shoenfeld Y, Toubi E. The autoimmune characteristics of progressive or sudden sensorineural hearing loss. Autoimmunity 2006; 39: 153-158
  • 74 Toubi E, Ben-David J, Kessel A, Halas K, Sabo E, Luntz M. Immune-mediated disorders associated with idiopathic sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 2004; 113: 445-449
  • 75 Hajas A, Szodoray P, Barath S , et al. Sensorineural hearing loss in patients with mixed connective tissue disease: immunological markers and cytokine levels. J Rheumatol 2009; 36: 1930-1936
  • 76 Hervier B, Bordure P, Audrain M, Calais C, Masseau A, Hamidou M. Systematic screening for nonspecific autoantibodies in idiopathic sensorineural hearing loss: no association with steroid response. Otol Neurotol 2010; 31: 687-690
  • 77 García-Berrocal JR, Ramírez-Camacho R, Millán I , et al. Sudden presentation of immune-mediated inner ear disease: characterization and acceptance of a cochleovestibular dysfunction. J Laryngol Otol 2003; 117: 775-779
  • 78 Deroee AF, Huang TC, Morita N, Hojjati M. Sudden hearing loss as the presenting symptom of systemic sclerosis. Otol Neurotol 2009; 30: 277-279
  • 79 Agrup C. Immune-mediated audiovestibular disorders in the paediatric population: a review. Int J Audiol 2008; 47: 560-565
  • 80 Trune DR, Kempton JB, Kessi M. Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope 2000; 110: 1902-1906
  • 81 Trune DR. Cochlear immunoglobulin in the C3H/lpr mouse model for autoimmune hearing loss. Otolaryngol Head Neck Surg 1997; 117: 504-508
  • 82 Lin DW, Trune DR. Breakdown of stria vascularis blood-labyrinth barrier in C3H/lpr autoimmune disease mice. Otolaryngol Head Neck Surg 1997; 117: 530-534
  • 83 Ruckenstein MJ, Milburn M, Hu L. Strial dysfunction in the MRL-Fas mouse. Otolaryngol Head Neck Surg 1999; 121: 452-456
  • 84 Trune DR, Kempton JB. Aldosterone and prednisolone control of cochlear function in MRL/MpJ-Fas(lpr) autoimmune mice. Hear Res 2001; 155: 9-20
  • 85 Trune DR, Larrain BE, Hausman FA, Kempton JB, MacArthur CJ. Simultaneous measurement of multiple ear proteins with multiplex ELISA assays. Hear Res 2011; 275: 1-7
  • 86 Adams JC. Clinical implications of inflammatory cytokines in the cochlea: a technical note. Otol Neurotol 2002; 23: 316-322
  • 87 Keles E, Gödekmerdan A, Kalidağ T , et al. Meniere's disease and allergy: allergens and cytokines. J Laryngol Otol 2004; 118: 688-693
  • 88 Cai Q, Du X, Zhou B, Cai C, Kermany MH, Yoo T. Induction of tolerance by oral administration of beta-tubulin in an animal model of autoimmune inner ear disease. ORL J Otorhinolaryngol Relat Spec 2009; 71: 135-141
  • 89 Takatsu M, Higaki M, Kinoshita H, Mizushima Y, Koizuka I. Ear involvement in patients with rheumatoid arthritis. Otol Neurotol 2005; 26: 755-761
  • 90 Süslü N, Yilmaz T, Gürsel B. Utility of immunologic parameters in the evaluation of Meniere's disease. Acta Otolaryngol 2009; 129: 1160-1165
  • 91 Süslü N, Yilmaz T, Gürsel B. Utility of anti-HSP 70, TNF-alpha, ESR, antinuclear antibody, and antiphospholipid antibodies in the diagnosis and treatment of sudden sensorineural hearing loss. Laryngoscope 2009; 119: 341-346
  • 92 Aminpour S, Tinling SP, Brodie HA. Role of tumor necrosis factor-alpha in sensorineural hearing loss after bacterial meningitis. Otol Neurotol 2005; 26: 602-609
  • 93 Fuse T, Hayashi T, Oota N , et al. Immunological responses in acute low-tone sensorineural hearing loss and Ménière's disease. Acta Otolaryngol 2003; 123: 26-31
  • 94 Selivanova O, Heinrich UR, Brieger J, Feltens R, Mann W. Fast alterations of vascular endothelial growth factor (VEGF) expression and that of its receptors (Flt-1, Flk-1 and Neuropilin) in the cochlea of guinea pigs after moderate noise exposure. Eur Arch Otorhinolaryngol 2007; 264: 121-128