Hereditary angioedema: a bradykinin-mediated swelling disorder

Jenny Björkqvist; Anna Sala-Cunill; Thomas Renné

doi:10.1160/TH12-08-0549

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(03): 368-374
DOI: 10.1160/TH12-08-0549

Theme Issue Article

Schattauer GmbH

Hereditary angioedema: a bradykinin-mediated swelling disorder

Jenny Björkqvist

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

,

Anna Sala-Cunill

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

³Allergy Section, Internal Medicine Department, Hospital Universitari Vall d´Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

⁴Allergy Research Unit, Allergy Department, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

,

Thomas Renné

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

Keywords

Contact phase - inflammatory mediators - proteases - SERPINs

Full Text

References

References
1 Schapira M, Silver LD, Scott CF. et al. Prekallikrein activation and high-molecular-weight kininogen consumption in hereditary angioedema. N Engl J Med 1983; 308: 1050-1053.
2 Joseph K, Tuscano TB, Kaplan AP. Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma. Ann Allergy Asthma Immunol 2008; 101: 279-286.
3 Han ED, MacFarlane RC, Mulligan AN. et al. Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Invest 2002; 109: 1057-1063.
4 Cugno M, Nussberger J, Cicardi M. et al. Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 2003; 3: 311-317.
5 Leeb-Lundberg LM, Marceau F, Muller-Esterl W. et al. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 2005; 57: 27-77.
6 Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med 2008; 359: 1027-1036.
7 Kaplan AP, Ghebrehiwet B. The plasma bradykinin-forming pathways and its interrelationships with complement. Mol Immunol 2010; 47: 2161-2169.
8 Renne T, Schuh K, Muller-Esterl W. Local bradykinin formation is controlled by glycosaminoglycans. J Immunol 2005; 175: 3377-3385.
9 Renne T, Gruber A. Plasma kallikrein: novel functions for an old protease. Thromb Haemost 2012; 107: 1012-1013.
10 Kitamura N, Takagaki Y, Furuto S. et al. A single gene for bovine high molecular weight and low molecular weight kininogens. Nature 1983; 305: 545-549.
11 Maurer M, Bader M, Bas M. et al. New topics in bradykinin research. Allergy 2011; 66: 1397-1406.
12 Renne T, Dedio J, Meijers JC. et al. Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2. J Biol Chem 1999; 274: 25777-25784.
13 Renne T. The procoagulant and proinflammatory plasma contact system. Semin Immunopathol 2012; 34: 31-41.
14 Davis AE, 3rd Lu F, Mejia P. C1 inhibitor, a multi-functional serine protease inhibitor. Thromb Haemost 2010; 104: 886-893.
15 Renne T, Dedio J, David G. et al. High molecular weight kininogen utilizes heparan sulfate proteoglycans for accumulation on endothelial cells. J Biol Chem 2000; 275: 33688-33696.
16 Renne T, Muller-Esterl W. Cell surface-associated chondroitin sulfate proteoglycans bind contact phase factor H-kininogen. FEBS Lett 2001; 500: 36-40.
17 Muller F, Renne T. Novel roles for factor XII-driven plasma contact activation system. Curr Opin Hematol 2008; 15: 516-521.
18 Mori K, Sakamoto W, Nagasawa S. Studies on human high molecular weight (HMW) kininogen. III. Cleavage of HMW kininogen by the action of human salivary kallikrein. J Biochem 1981; 90: 503-509.
19 Colman RW, Schmaier AH. Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood 1997; 90: 3819-3843.
20 Muller F, Gailani D, Renne T. Factor XI and XII as antithrombotic targets. Curr Opin Hematol 2011; 18: 349-355.
21 Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44: 1-80.
22 Kaplan AP, Joseph K, Silverberg M. Pathways for bradykinin formation and inflammatory disease. J Allergy Clin Immunol 2002; 109: 195-209.
23 Takada Y, Skidgel RA, Erdos EG. Purification of human urinary prokallikrein. Identification of the site of activation by the metalloproteinase thermolysin. Biochem J 1985; 232: 851-858.
24 Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22: 184-204.
25 Sainz IM, Pixley RA, Colman RW. Fifty years of research on the plasma kallikrein-kinin system: from protein structure and function to cell biology and in-vivo pathophysiology. Thromb Haemost 2007; 98: 77-83.
26 Herwald H, Renne T, Meijers JC. et al. Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. J Biol Chem 1996; 271: 13061-13067.
27 Vogel R, Kaufmann J, Chung DW. et al. Mapping of the prekallikrein-binding site of human H-kininogen by ligand screening of lambda gt11 expression libraries. Mimicking of the predicted binding site by anti-idiotypic antibodies. J Biol Chem 1990; 265: 12494-12502.
28 Marcondes S, Antunes E. The plasma and tissue kininogen-kallikrein-kinin system: role in the cardiovascular system. Curr Med Chem Cardiovasc Hematol Agents 2005; 3: 33-44.
29 Meneton P, Bloch-Faure M, Hagege AA. et al. Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice. Proc Natl Acad Sci USA 2001; 98: 2634-2639.
30 Kariya K, Yamauchi A. Relationship between hypertensive response and brain kinin level in the rat injected intraventricularly with glandular kallikrein. Jpn J Pharmacol 1987; 43: 129-132.
31 Liao JK, Homcy CJ. The G proteins of the G alpha i and G alpha q family couple the bradykinin receptor to the release of endothelium-derived relaxing factor. J Clin Invest 1993; 92: 2168-2172.
32 Yang CM, Tsai YJ, Pan SL. et al. Pharmacological and functional characterisation of bradykinin receptors in rat cultured vascular smooth muscle cells. Cell Signal 1999; 11: 853-862.
33 Marceau F, Hess JF, Bachvarov DR. The B1 receptors for kinins. Pharmacol Rev 1998; 50: 357-386.
34 Bossi F, Fischetti F, Regoli D. et al. Novel pathogenic mechanism and therapeutic approaches to angioedema associated with C1 inhibitor deficiency. J Allergy Clin Immunol 2009; 124: 1303-1310 e4
35 Raslan F, Schwarz T, Meuth SG. et al. Inhibition of bradykinin receptor B1 protects mice from focal brain injury by reducing blood-brain barrier leakage and inflammation. J Cereb Blood Flow Metab 2010; 30: 1477-1486.
36 Benz PM, Blume C, Seifert S. et al. Differential VASP phosphorylation controls remodeling of the actin cytoskeleton. J Cell Sci 2009; 122: 3954-3965.
37 Benz PM, Blume C, Moebius J. et al. Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. J Cell Biol 2008; 180: 205-219.
38 Tiruppathi C, Ahmmed GU, Vogel SM. et al. Ca2+ signalling, TRP channels, and endothelial permeability. Microcirculation 2006; 13: 693-708.
39 Kim YM, Renne C, Seifert S. et al. Impaired melanoma growth in VASP deficient mice. FEBS Lett 2011; 585: 2533-2536.
40 LaRusch GA, Mahdi F, Shariat-Madar Z. et al. Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis. Blood 2010; 115: 5111-5120.
41 Busse R, Fleming I. Regulation of endothelium-derived vasoactive autacoid production by hemodynamic forces. Trends Pharmacol Sci 2003; 24: 24-29.
42 Lindsay SL, Ramsey S, Aitchison M. et al. Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239. J Cell Sci 2007; 120: 3011-3021.
43 Wojciak-Stothard B, Torondel B, Zhao L. et al. Modulation of Rac1 activity by ADMA/DDAH regulates pulmonary endothelial barrier function. Mol Biol Cell 2009; 20: 33-42.
44 Shigematsu S, Ishida S, Gute DC. et al. Bradykinin-induced proinflammatory signalling mechanisms. Am J Physiol Heart Circ Physiol 2002; 283: H2676-2686.
45 Frick IM, Akesson P, Herwald H. et al. The contact system--a novel branch of innate immunity generating antibacterial peptides. EMBO J 2006; 25: 5569-5578.
46 Skidgel RA. Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. J Cardiovasc Pharmacol 1992; 20 (Suppl. 09) S4-9.
47 Sheikh IA, Kaplan AP. Studies of the digestion of bradykinin, Lys-bradykinin, and des-Arg9-bradykinin by angiotensin converting enzyme. Biochem Pharmacol 1986; 35: 1951-1956.
48 Kokkonen JO, Lindstedt KA, Kuoppala A. et al. Kinin-degrading pathways in the human heart. Trends Cardiovasc Med 2000; 10: 42-45.
49 Renne T, Schmaier AH, Nickel KF. et al. In vivo roles of factor XII. Blood. 2012 epub ahead of print
50 Cugno M, Cicardi M, Bottasso B. et al. Activation of the coagulation cascade in C1-inhibitor deficiencies. Blood 1997; 89: 3213-3218.
51 Oschatz C, Maas C, Lecher B. et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 2011; 34: 258-268.
52 Nussberger J, Cugno M, Cicardi M. Bradykinin-mediated angioedema. N Engl J Med 2002; 347: 621-622.
53 Banerji A, Clark S, Blanda M. et al. Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. Ann Allergy Asthma Immunol 2008; 100: 327-332.
54 Ricketti AJ, Cleri DJ, Ramos-Bonner LS. et al. Hereditary angioedema presenting in late middle age after angiotensin-converting enzyme inhibitor treatment. Ann Allergy Asthma Immunol 2007; 98: 397-401.
55 Cicardi M, Levy RJ, McNeil DL. et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med 2010; 363: 523-531.
56 Caballero T, Baeza ML, Cabanas R. et al. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part I Classification, epidemiology, pathophysiology, genetics, clinical symptoms, and diagnosis. J Investig Allergol Clin Immunol 2011; 21: 333-347.
57 Davis 3rd. AE. Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol 2008; 100 (01) (Suppl. 02) S7-12.
58 Stoppa-Lyonnet D, Tosi M, Laurent J. et al. Altered C1 inhibitor genes in type I hereditary angioedema. N Engl J Med 1987; 317: 1-6.
59 Bowen B, Hawk JJ, Sibunka S. et al. A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations. Clin Immunol 2001; 98: 157-163.
60 Kalmar L, Bors A, Farkas H. et al. Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema. Hum Mutat 2003; 22: 498.
61 Donaldson VH, Bissler JJ. C1- inhibitors and their genes: an update. J Lab Clin Med 1992; 119: 330-333.
62 Bork K, Barnstedt SE, Koch P. et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet 2000; 356: 213-217.
63 Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun 2006; 343: 1286-1289.
64 Cichon S, Martin L, Hennies HC. et al. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet 2006; 79: 1098-1104.
65 Bork K, Wulff K, Meinke P. et al. A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor. Clin Immunol 2011; 141: 31-35.
66 Muller F, Mutch NJ, Schenk WA. et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 2009; 139: 1143-1156.
67 Maas C, Govers-Riemslag JW, Bouma B. et al. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest 2008; 118: 3208-3218.
68 Kannemeier C, Shibamiya A, Nakazawa F. et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 2007; 104: 6388-6393.
69 Pauer HU, Renne T, Hemmerlein B. et al. Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo. Thromb Haemost 2004; 92: 503-508.
70 Iwaki T, Castellino FJ. Plasma levels of bradykinin are suppressed in factor XII-deficient mice. Thromb Haemost 2006; 95: 1003-1010.
71 Blossom DB, Kallen AJ, Patel PR. et al. Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med 2008; 359: 2674-2684.
72 Guerrini M, Beccati D, Shriver Z. et al. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat Biotechnol 2008; 26: 669-675.
73 Kishimoto TK, Viswanathan K, Ganguly T. et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med 2008; 358: 2457-2467.
74 Muller F, Renne T. Platelet polyphosphates: The nexus of primary and secondary hemostasis. Scand J Clin Lab Invest 2011; 71: 82-86.
75 Moreno-Sanchez D, Hernandez-Ruiz L, Ruiz FA. et al. Polyphosphate is a novel pro-inflammatory regulator of mast cells and is located in acidocalcisomes. J Biol Chem. 2012 epub ahead of print
76 Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med 2001; 161: 2417-2429.
77 Maas C, Renne T. Regulatory mechanisms of the plasma contact system. Thromb Res 2012; 129 (Suppl. 02) S73-76.
78 Johne J, Blume C, Benz PM. et al. Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma. Biol Chem 2006; 387: 173-178.
79 Zuraw B, Cicardi M, Levy RJ. et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol 2010; 126: 821-827 e14
80 Cicardi M, Banerji A, Bracho F. et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med 2010; 363: 532-541.
81 Cicardi M, Bork K, Caballero T. et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy 2012; 67: 147-157.
82 Zuraw BL, Busse PJ, White M. et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med 2010; 363: 513-522.
83 Austinat M, Braeuninger S, Pesquero JB. et al. Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema. Stroke 2009; 40: 285-293.
84 Bouillet L, Longhurst H, Boccon-Gibod I. et al. Disease expression in women with hereditary angioedema. Am J Obstet Gynecol 2008; 199 (484) e1-4
85 Bouillet L, Ponard D, Drouet C. et al. Non-histaminic angiodema management: diagnostic and therapeutic interest of tranexamic acid. Rev Med Interne 2004; 25: 924-926.
86 Bouillet L, Boccon-Gibod I, Ponard D. et al. Bradykinin receptor 2 antagonist (icatibant) for hereditary angioedema type III attacks. Ann Allergy Asthma Immunol 2009; 103: 448.
87 Bork K, Wulff K, Hardt J. et al. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol 2009; 124: 129-134.
88 Vitrat-Hincky V, Gompel A, Dumestre-Perard C. et al. Type III hereditary angio-oedema: clinical and biological features in a French cohort. Allergy 2010; 65: 1331-1336.
89 Bork K, Fischer B, Dewald G. Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Am J Med 2003; 114: 294-298.
90 Renne T, Pozgajova M, Gruner S. et al. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med 2005; 202: 271-281.
91 Revenko AS, Gao D, Crosby JR. et al. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood 2011; 118: 5302-5311.
92 Pixley RA, De La Cadena R, Page JD. et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 91: 61-68.
93 Food and Drug Administration (FDA). Post-market drug safety information for patients and providers. Available at: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm112597.htm