AIMS/HYPOTHESIS: We measured components of the kallikrein- kinin system in human type 2 diabetes mellitus and the effects of statin therapy on the circulating kallikrein-kinin system. METHODS: Circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, as well as plasma and tissue kallikrein, and kallistatin were measured in non-diabetic and diabetic patients before coronary artery bypass graft surgery. Tissue kallikrein levels in atrial tissue were examined by immunohistochemistry and atrial tissue kallikrein mRNA quantified. RESULTS: Plasma levels of tissue kallikrein were approximately 62% higher in diabetic than in non-diabetic patients (p=0.001), whereas no differences were seen in circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, or in plasma kallikrein or kallistatin. Immunohistochemistry revealed a twofold increase in tissue kallikrein levels in atrial myocytes (p= 0.015), while tissue kallikrein mRNA levels were increased eightfold in atrial tissue of diabetic patients (p=0.014). Statin therapy did not change any variables of the circulating kallikrein-kinin system. Neither aspirin, calcium antagonists, beta blockers or long-acting nitrate therapies influenced any kallikrein-kinin system variable. CONCLUSIONS/ INTERPRETATION: Tissue kallikrein levels are increased in type 2 diabetes, whereas statin therapy does not modify the circulating kallikrein-kinin system. Cardiac tissue kallikrein may play a greater cardioprotective role in type 2 diabetic than in non-diabetic patients and contribute to the benefits of ACE inhibitor therapy in type 2 diabetic patients. However, our findings do not support a role for the kallikrein-kinin system in mediating the effects of statin therapy on endothelial function.
AIMS/HYPOTHESIS: We measured components of the kallikrein- kinin system in human type 2 diabetes mellitus and the effects of statin therapy on the circulating kallikrein-kinin system. METHODS: Circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, as well as plasma and tissue kallikrein, and kallistatin were measured in non-diabetic and diabeticpatients before coronary artery bypass graft surgery. Tissue kallikrein levels in atrial tissue were examined by immunohistochemistry and atrial tissue kallikrein mRNA quantified. RESULTS: Plasma levels of tissue kallikrein were approximately 62% higher in diabetic than in non-diabeticpatients (p=0.001), whereas no differences were seen in circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, or in plasma kallikrein or kallistatin. Immunohistochemistry revealed a twofold increase in tissue kallikrein levels in atrial myocytes (p= 0.015), while tissue kallikrein mRNA levels were increased eightfold in atrial tissue of diabeticpatients (p=0.014). Statin therapy did not change any variables of the circulating kallikrein-kinin system. Neither aspirin, calcium antagonists, beta blockers or long-acting nitrate therapies influenced any kallikrein-kinin system variable. CONCLUSIONS/ INTERPRETATION: Tissue kallikrein levels are increased in type 2 diabetes, whereas statin therapy does not modify the circulating kallikrein-kinin system. Cardiac tissue kallikrein may play a greater cardioprotective role in type 2 diabetic than in non-diabeticpatients and contribute to the benefits of ACE inhibitor therapy in type 2 diabeticpatients. However, our findings do not support a role for the kallikrein-kinin system in mediating the effects of statin therapy on endothelial function.
Authors: W Huang; Y Gallois; N Bouby; P Bruneval; D Heudes; M F Belair; J H Krege; P Meneton; M Marre; O Smithies; F Alhenc-Gelas Journal: Proc Natl Acad Sci U S A Date: 2001-10-30 Impact factor: 11.205
Authors: M Marre; X Jeunemaitre; Y Gallois; M Rodier; G Chatellier; C Sert; L Dusselier; Z Kahal; L Chaillous; S Halimi; A Muller; H Sackmann; B Bauduceau; F Bled; P Passa; F Alhenc-Gelas Journal: J Clin Invest Date: 1997-04-01 Impact factor: 14.808
Authors: Anne Pizard; Christine Richer; Nadine Bouby; Nicolas Picard; Pierre Meneton; Michel Azizi; François Alhenc-Gelas Journal: Biol Chem Date: 2008-06 Impact factor: 3.915
Authors: Jiayi Yao; Pierre J Guihard; Ana M Blazquez-Medela; Yina Guo; Jeremiah H Moon; Medet Jumabay; Kristina I Boström; Yucheng Yao Journal: Circ Res Date: 2015-08-11 Impact factor: 17.367
Authors: Duncan J Campbell; Jithendra B Somaratne; Alicia J Jenkins; David L Prior; Michael Yii; James F Kenny; Andrew E Newcomb; Casper G Schalkwijk; Mary J Black; Darren J Kelly Journal: Cardiovasc Diabetol Date: 2011-09-19 Impact factor: 9.951
Authors: Pierre J Guihard; Jiayi Yao; Ana M Blazquez-Medela; Luisa Iruela-Arispe; Kristina I Boström; Yucheng Yao Journal: PLoS One Date: 2016-12-09 Impact factor: 3.240
Authors: John T Heiker; Nora Klöting; Peter Kovacs; E Bartholomeus Kuettner; Norbert Sträter; Stephan Schultz; Matthias Kern; Michael Stumvoll; Matthias Blüher; Annette G Beck-Sickinger Journal: Cell Mol Life Sci Date: 2013-01-31 Impact factor: 9.261