title: Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney.
abstract: Tissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many organs including arteries and kidney. Study of the physiological role of KLK1 has benefited from the availability of mouse and human genetic models of KLK1 deficiency, through engineering of KLK1 mouse mutants and discovery of a major polymorphism in the human KLK1 gene that induces a loss of enzyme activity. Studies in KLK1-deficient mice and human subjects partially deficient in KLK1 have documented its critical role in arterial function in both species. KLK1 is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated. Studies of experimental diseases in KLK1-deficient mice have revealed cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes. Potential clinical and therapeutic developments are discussed.
authors.affiliation: INSERM U652/U872, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, F-75006 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pizard
authors.forename: Christine
authors.initials: C
authors.lastname: Richer
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
mesh_terms: D000818:Animals; D001158:Arteries / Q000201:enzymology / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020840:Tissue Kallikreins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: D020840:Tissue Kallikreins