Increased tissue kallikrein levels in type 2 diabetes.

Abstract

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.

• Authors: D J Campbell, A Kladis, Y Zhang, A J Jenkins, D L Prior, M Yii, J F Kenny, M J Black, D J Kelly
• Journal: Diabetologia (Diabetologia) Vol. 53 Issue 4 Pg. 779-85 (Apr 2010) ISSN: 1432-0428 [Electronic] Germany
• PMID: 20225398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Cardiotonic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• RNA, Messenger
• Tissue Kallikreins

Topics

• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Cardiotonic Agents (blood)
• Coronary Artery Bypass
• Diabetes Mellitus, Type 2 (blood, enzymology)
• Diabetic Angiopathies (blood, drug therapy, surgery)
• Endothelium, Vascular (drug effects, physiopathology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Immunohistochemistry
• RNA, Messenger (genetics)
• Tissue Kallikreins (blood, genetics)