Tags

Type your tag names separated by a space and hit enter

Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man.
Thromb Haemost. 2013 Sep; 110(3):476-83.TH

Abstract

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.

Authors+Show Affiliations

Francois Alhenc-Gelas, INSERM U872, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine 75006 Paris, France, E-mail: francois.alhenc-gelas@inserm.fr.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23572029

Citation

Waeckel, L, et al. "Pathophysiology of Genetic Deficiency in Tissue Kallikrein Activity in Mouse and Man." Thrombosis and Haemostasis, vol. 110, no. 3, 2013, pp. 476-83.
Waeckel L, Potier L, Richer C, et al. Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man. Thromb Haemost. 2013;110(3):476-83.
Waeckel, L., Potier, L., Richer, C., Roussel, R., Bouby, N., & Alhenc-Gelas, F. (2013). Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man. Thrombosis and Haemostasis, 110(3), 476-83. https://doi.org/10.1160/TH12-12-0937
Waeckel L, et al. Pathophysiology of Genetic Deficiency in Tissue Kallikrein Activity in Mouse and Man. Thromb Haemost. 2013;110(3):476-83. PubMed PMID: 23572029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man. AU - Waeckel,L, AU - Potier,L, AU - Richer,C, AU - Roussel,R, AU - Bouby,N, AU - Alhenc-Gelas,F, Y1 - 2013/04/04/ PY - 2012/12/20/received PY - 2013/03/14/accepted PY - 2013/4/11/entrez PY - 2013/4/11/pubmed PY - 2014/4/10/medline SP - 476 EP - 83 JF - Thrombosis and haemostasis JO - Thromb. Haemost. VL - 110 IS - 3 N2 - 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. SN - 2567-689X UR - https://www.unboundmedicine.com/medline/citation/23572029/Pathophysiology_of_genetic_deficiency_in_tissue_kallikrein_activity_in_mouse_and_man_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1160/TH12-12-0937 DB - PRIME DP - Unbound Medicine ER -