CP/CPB and DM are both associated with up-regulation in V1 receptor expression/localization in human myocardium. Vasopressin may induce coronary arteriolar constriction via V1A. This alteration may lead to increased coronary arteriolar spasm in patients with DM undergoing CP/CPB and cardiac surgery.
Objectives
We investigated the changes in adherens-junction-proteins, such as vascular endothelial (VE)-cadherin and β-catenin of skeletal muscle and vessels in patients with or without diabetes in the setting of CPB and cardiac surgery.
Methods
Skeletal muscle tissue samples were harvested pre- and post-CPB from non-diabetic (ND) (HgbA1c: 5.4 ± 0.1), controlled diabetic (CDM) (HgbA1c: 6.3 ± 0.1), and uncontrolled diabetic patients (UDM) (HgbA1c: 9.6 ± 0.3) undergoing CABG surgery (n = 8/group). The expression/phosphorylation of adherens-junction-proteins VE-cadherin and β-catenin were assessed by immunoblotting and immuno-histochemistry. Endothelial function of skeletal muscle arterioles was determined by videomicroscopy in response to the vasodilator substance P.
Results
The protein expression of total VE-cadherin was not changed at baseline or between pre- and post-CPB among groups. The pre-CPB level of phospho-VE-cadherin was found to be significantly increased in the UDM group compared with the ND or CDM groups (P <0.05). The post-CPB levels of phospho-VE-cadherin were significantly increased as compared with pre-CPB in all groups (P <0.05 each), and this increase was greater in the UDM group than that of the ND or CDM groups (P<0.05). Expression of basal β-catenin protein in UDM group was decreased as compared with ND or CDM (P<0.05). There were significant decreases in the β-catenin protein expression between pre- and post-CPB in all three groups (P<0.05 each) and this decrease was greater in the UDM group than the ND group (P<0.05). There were decreases in the relaxation response of skeletal muscle arterioles to substance P after CPB in all three groups (P<0.05), and this alteration was more pronounced in the UDM patients (P<0.05).
Conclusion
Uncontrolled diabetes causes inactivation and reduction in the expression of endothelial adherens-junction-protein in the arterioles of skeletal muscle early after CPB. The enhanced phosphorylation of VE-cadherin and degradation of β-catenin indicate deterioration of these proteins and damage of the cell-cell endothelial junctions, specifically in the diabetic peripheral vessels. These alterations may contribute to the increases in peripheral vascular permeability and endothelial dysfunction.
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