Subscribe to RSS
DOI: 10.1160/TH12-12-0937
Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man
Financial Support: This work was supported by Institut National de la Sante et de la Recherche medicale, Paris-Descartes University, the European Vascular Genomics Network, a Network of Excellence supported by the European Community’s sixth Framework Program for Research Priority 1“Life sciences, genomics and biotechnology for health” (LSHMCT-2003-503254), the National Research Agency (ANR 05-PCOD-027), and the French Society of Nephrology and the French Diabetes Society.Publication History
Received:
20 December 2012
Accepted after major revision:
14 March 2013
Publication Date:
22 November 2017 (online)
Summary
Study of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.
-
References
- 1 Abelous JE, Bardier E. Les substances hypotensives de l′urine humaine normale. Comptes Rendus Société Biologie 1909; 66: 511-520.
- 2 Frey EK, Kraut H. Über einen von der Niere ausgeschiedenen, die Herztätigkeit anregenden Stoff. Hoppe-Seyler Z Physiol Chem 1926; 157: 32-61.
- 3 Alhenc-Gelas F, Girolami J. Molecular and genetic aspects of the kallikrein-kinin sytem. In: Kinins. Berlin: De Gruyter Gmbh; 2011. pp. 7-32.
- 4 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.
- 5 Slim R, Torremocha F, Moreau T. et al. Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. J Am Soc Nephrol 2002; 13: 968-976.
- 6 Pizard A, Richer C, Bouby N. et al. Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney. Biol Chem 2008; 389: 701-706.
- 7 Diamandis EP, Yousef GM, Clements J. et al. New nomenclature for the human tissue kallikrein gene family. Clin Chem 2000; 46: 1855-1858.
- 8 Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22: 184-204.
- 9 Mason AJ, Evans BA, Cox DR. et al. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature 1983; 303: 300-307.
- 10 Clements JA. Reflections on the tissue kallikrein and kallikrein-related peptidase family - from mice to men - what have we learnt in the last two decades?. Biol Chem 2008; 389: 1447-1454.
- 11 Brillard-Bourdet M, Moreau T, Gauthier F. Substrate specificity of tissue kallikreins: importance of an extended interaction site. Biochim Biophys Acta 1995; 1246: 47-52.
- 12 Harvey TJ, Hooper JD, Myers SA. et al. Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem 2000; 275: 37397-37406.
- 13 Katz BA, Liu B, Barnes M. et al. Crystal structure of recombinant human tissue kallikrein at 2.0 A resolution. Protein Sci 1998; 07: 875-885.
- 14 Hecquet C, Tan F, Marcic BM. et al. Human bradykinin B(2) receptor is activated by kallikrein and other serine proteases. Mol Pharmacol 2000; 58: 828-836.
- 15 Picard N, Van Abel M, Campone C. et al. Tissue kallikrein-deficient mice display a defect in renal tubular calcium absorption. J Am Soc Nephrol 2005; 16: 3602-3610.
- 16 Picard N, Eladari D, El Moghrabi S. et al. Defective ENaC Processing and Function in Tissue Kallikrein-deficient Mice. J Biol Chem 2008; 283: 4602-4611.
- 17 El Moghrabi S, Houillier P, Picard N. et al. Tissue kallikrein permits early renal adaptation to potassium load. Proc Natl Acad Sci USA 2010; 107: 13526-13531.
- 18 Patel AB, Chao J, Palmer LG. Tissue kallikrein activation of the epithelial Na channel. Am J Physiol Renal Physiol 2012; 303: F540-F550.
- 19 Beaubien G, Rosinski-Chupin I, Mattei MG. et al. Gene structure and chromosomal localisation of plasma kallikrein. Biochemistry 1991; 30: 1628-1635.
- 20 Joseph K, Kaplan A. Formation of Bradykinin: A Major Contributor to the Innate Inflammatory Response. Adv Immmunol 2005; 86: 159-208.
- 21 Iwaki T, Castellino FJ. Plasma levels of bradykinin are suppressed in factor XII-deficient mice. Thromb Haemost 2006; 95: 1003-1010.
- 22 Maas C, Oschatz C, Renne T. The plasma contact system 2.0. Semin Thromb Hemost 2011; 37: 375-381.
- 23 Joseph K, Tholanikunnel BG, Kaplan AP. Heat shock protein 90 catalyses activation of the prekallikrein-kininogen complex in the absence of factor XII. Proc Natl Acad Sci USA 2002; 99: 896-900.
- 24 Shariat-Madar Z, Mahdi F, Schmaier AH. Identification and characterisation of prolylcarboxypeptidase as an endothelial cell prekallikrein activator. J Biol Chem 2002; 277: 17962-17969.
- 25 Joseph K, Tholanikunnel BG, Kaplan AP. Factor XII-independent cleavage of high-molecular-weight kininogen by prekallikrein and inhibition by C1 inhibitor. J Allergy Clin Immunol 2009; 124: 143-149.
- 26 Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44: 1-80.
- 27 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.
- 28 Brown NJ, Gainer JV, Murphey LJ. et al. Bradykinin stimulates tissue plasminogen activator release from human forearm vasculature through B(2) receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Circulation 2000; 102: 2190-2196.
- 29 Borkowski JA, Ransom RW, Seabrook GR. et al. Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. J Biol Chem 1995; 270: 13706-13710.
- 30 Linz W, Wiemer G, Gohlke P. et al. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev 1995; 47: 25-49.
- 31 Pizard A, Marchetti J, Allegrini J. et al. Negative cooperativity in the human bradykinin B2 receptor. J Biol Chem 1998; 273: 1309-1315.
- 32 Griol-Charhbili V, Messadi-Laribi E, Bascands JL. et al. Role of tissue kallikrein in the cardioprotective effects of ischaemic and pharmacological preconditioning in myocardial ischaemia. Faseb J 2005; 19: 1172-1174.
- 33 Kakoki M, McGarrah RW, Kim HS. et al. Bradykinin B1 and B2 receptors both have protective roles in renal ischaemia/reperfusion injury. Proc Natl Acad Sci USA 2007; 104: 7576-7581.
- 34 Bodin S, Chollet C, Goncalves-Mendes N. et al. Kallikrein protects against microalbuminuria in experimental type I diabetes. Kidney Int 2009; 76: 395-403.
- 35 Regoli DC, Marceau F, Lavigne J. Induction of beta 1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide. Eur J Pharmacol 1981; 71: 105-115.
- 36 Duka I, Kintsurashvili E, Gavras I. et al. Vasoactive potential of the b(1) bradykinin receptor in normotension and hypertension. Circ Res 2001; 88: 275-281.
- 37 Cayla C, Todiras M, Iliescu R. et al. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension. Faseb J 2007; 21: 1689-1698.
- 38 Bergaya S, Meneton P, Bloch-Faure M. et al. Decreased flow-dependent dilation in carotid arteries of tissue kallikrein-knockout mice. Circ Res 2001; 88: 593-599.
- 39 Zinner SH, Margolius HS, Rosner B. et al. Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes. Am J Epidemiol 1976; 104: 124-132.
- 40 Berry TD, Hasstedt SJ, Hunt SC. et al. A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. Hypertension 1989; 13: 3-8.
- 41 Song Q, Chao J, Chao L. DNA polymorphisms in the 5′-flanking region of the human tissue kallikrein gene. Hum Genet 1997; 99: 727-734.
- 42 Hilgers RH, Bergaya S, Schiffers PM. et al. Uterine artery structural and functional changes during pregnancy in tissue kallikrein-deficient mice. Arterioscler Thromb Vasc Biol 2003; 23: 1826-1832.
- 43 Bergaya S, Matrougui K, Meneton P. et al. Role of tissue kallikrein in response to flow in mouse resistance arteries. J Hypertens 2004; 22: 745-750.
- 44 Bergaya S, Hilgers RH, Meneton P. et al. Flow-dependent dilation mediated by endogenous kinins requires angiotensin AT2 receptors. Circ Res 2004; 94: 1623-1629.
- 45 Azizi M, Boutouyrie P, Bissery A. et al. Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans. J Clin Invest 2005; 115: 780-787.
- 46 Rossi GP, Taddei S, Ghiadoni L. et al. Tissue kallikrein gene polymorphisms induce no change in endothelium-dependent or independent vasodilation in hypertensive and normotensive subjects. J Hypertens 2006; 24: 1955-1963.
- 47 Nolly H, Scicli AG, Scicli G. et al. Characterisation of a kininogenase from rat vascular tissue resembling tissue kallikrein. Circ Res 1985; 56: 816-821.
- 48 Marchetti J, Imbert-Teboul M, Alhenc-Gelas F. et al. Kallikrein along the rabbit microdissected nephron: a micromethod for its measurement. Effect of adrenalectomy and DOCA treatment. Pflugers Arch 1984; 401: 27-33.
- 49 Blanchard A, Azizi M, Peyrard S. et al. Partial human genetic deficiency in tissue kallikrein activity and renal calcium handling. Clin J Am Soc Nephrol 2007; 02: 320-325.
- 50 Shimamoto K, Mayfield RK, Margolius HS. et al. Immunoreactive tissue kallikrein in human serum. J Lab Clin Med 1984; 103: 731-738.
- 51 Azizi M, Emanueli C, Peyrard S. et al. Genetic and dietary control of plasma tissue kallikrein secretion and urinary kinins exretion in man. J Hypertens 2008; 26: 714-720.
- 52 Carretero OA, Carbini LA, Scicli AG. The molecular biology of the kallikrein-kinin system: I. General description, nomenclature and the mouse gene family. J Hypertens 1993; 11: 693-697.
- 53 Scicli AG, Carbini LA, Carretero OA. The molecular biology of the kallikrein-kinin system: II. The rat gene family. J Hypertens 1993; 11: 775-780.
- 54 Margolius HS, Geller R, De Jong W. et al. Altered urinary kallikrein excretion in rats with hypertension. Circ Res 1972; 30: 358-362.
- 55 Margolius HS, Horwitz D, Pisano JJ. et al. Relationships among urinary kallikrein, mineralocorticoids and human hypertensive disease. Fed Proc 1976; 35: 203-206.
- 56 Trabold F, Pons S, Hagege AA. et al. Cardiovascular phenotypes of kinin B2 receptor- and tissue kallikrein-deficient mice. Hypertension 2002; 40: 90-95.
- 57 Waeckel L, Potier L, Chollet C. et al. Antihypertensive role of tissue kallikrein in hyperaldosteronism in the mouse. Endocrinology 2012; 153: 3886-3896.
- 58 Griol-Charhbili V, Sabbah L, Colucci J. et al. Tissue kallikrein deficiency and renovascular hypertension in the mouse. Am J Physiol Regul Integr Comp Physiol 2009; 296: R1385-R1391.
- 59 Messadi E, Vincent MP, Griol-Charhbili V. et al. Genetically determined angiotensin converting enzyme level and myocardial tolerance to ischaemia. Faseb J 2010; 24: 4691-4700.
- 60 Messadi-Laribi E, Griol-Charhbili V, Pizard A. et al. Tissue kallikrein is involved in the cardioprotective effect of AT1-receptor blockade in acute myocardial ischaemia. J Pharmacol Exp Ther 2007; 323: 210-216.
- 61 Yang XP, Liu YH, Mehta D. et al. Diminished cardioprotective response to inhibition of angiotensin-converting enzyme and angiotensin II type 1 receptor in B(2) kinin receptor gene knockout mice. Circ Res 2001; 88: 1072-1079.
- 62 Siragy HM, de Gasparo M, Carey RM. Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000; 35: 1074-1077.
- 63 Sato M, Engelman RM, Otani H. et al. Myocardial protection by preconditioning of heart with losartan, an angiotensin II type 1-receptor blocker: implication of bradykinin-dependent and bradykinin-independent mechanisms. Circulation 2000; 102 (19) (Suppl. 03) III346-III351.
- 64 Abadir PM, Periasamy A, Carey RM. et al. Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerisation. Hypertension 2006; 48: 316-322.
- 65 Pons S, Griol-Charhbili V, Heymes C. et al. Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice. Eur J Heart Fail 2008; 10: 343-351.
- 66 Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. Br Med J (Clin Res Ed) 1987; 294: 1651-1654.
- 67 Huang W, Gallois Y, Bouby N. et al. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci USA 2001; 98: 13330-13334.
- 68 Kakoki M, Takahashi N, Jennette JC. et al. Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor. Proc Natl Acad Sci USA 2004; 101: 13302-13305.
- 69 Marre M, Bernadet P, Gallois Y. et al. Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 1994; 43: 384-388.
- 70 Marre M, Jeunemaitre X, Gallois Y. et al. Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group. J Clin Invest 1997; 99: 1585-1595.
- 71 Kakoki M, Kizer CM, Yi X. et al. Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors. J Clin Invest 2006; 116: 1302-1309.
- 72 Stone OA, Richer C, Emanueli C. et al. Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularisation. Arterioscler Thromb Vasc Biol 2009; 29: 657-664.
- 73 Krankel N, Katare RG, Siragusa M. et al. Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularisation potential. Circ Res 2008; 103: 1335-1343.
- 74 Spinetti G, Fortunato O, Cordella D. et al. Tissue kallikrein is essential for invasive capacity of circulating proangiogenic cells. Circ Res 2011; 108: 284-293.
- 75 Silvestre JS, Bergaya S, Tamarat R. et al. Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway. Circ Res 2001; 89: 678-683.
- 76 Cambien F, Poirier O, Lecerf L. et al. Deletion Polymorphism in the Gene for Angiotensin-Converting Enzyme Is a Potent Risk Factor for Myocardial-Infarction. Nature 1992; 359: 641-644.
- 77 Yusuf S, Sleight P, Pogue J. et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145-153.
- 78 Alhenc-Gelas F, Bouby N, Richer C. et al. Kinins as therapeutic agents in cardiovascular and renal diseases. Curr Pharm Des 2011; 17: 2654-2662.