Increased tissue kallikrein levels in type 2 diabetes.
OBJECTIVE
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
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.
Campbell
D J
DJ
St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. dcampbell@svi.edu.au
Kladis
A
A
Zhang
Y
Y
Jenkins
A J
AJ
Prior
D L
DL
Yii
M
M
Kenny
J F
JF
Black
M J
MJ
Kelly
D J
DJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000097:blood; D001026:Coronary Artery Bypass; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics; D020840:Tissue Kallikreins / Q000097:blood* / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D020840:Tissue Kallikreins