Differential impairment of adherens-junction expression/phosphorylation after cardioplegia in diabetic versus non-diabetic patients

These data suggest that poorly controlled diabetes down-regulates endothelial adherens-junction protein activation/expression/localization in the setting of CP/CPB. The increased tyrosine phosphorylation and deterioration of VE-cadherin indicate the damage of the cell-cell endothelial junctions in the diabetic vessels undergoing CP/CPB and cardiac surgery. These alterations may lead to increase in vascular permeability and endothelial dysfunction and affect outcomes in diabetic patients after cardiac surgery.

Right atrial tissue was harvested pre- and post-CP/CPB from non-diabetic (ND) [haemoglobin A1c (HbA1c): 5.4 ± 0.15], controlled (CDM) (HbA1c: 6.3 ± 0.14) and uncontrolled diabetic (UDM) (HbA1c: 9.9 ± 0.72) patients (n = 10/group). Expression/phosphorylation/localization of VE-cadherin, β- and γ-catenin were assessed by immunoblotting, immunoprecipitation and immunohistochemistry. In vitro atrial microvascular reactivity was assessed by videomicroscopy in response to the endothelium-dependent vasodilator adenosine 5'-diphosphate (ADP).

There were no significant differences in VE-cadherin protein expression between pre- and post-CP/CPB among groups. There were significant decreases in VE-cadherin densities in vessels of the UDM group versus the ND group at baseline or post-CP/CPB, respectively (P < 0.05). The level of basal phosphorylated VE-cadherin tends to be higher in the UDM compared with the ND group (P < 0.05). CP/CPB induced more phosphorylation of VE-cadherin in all groups (versus pre-CP/CPB; P < 0.05, respectively) and this effect was more pronounced in the UDM group (P < 0.05 versus ND or CDM). The protein levels of both catenins (β and γ) were lower in post-CP/CPB in UDM than ND patients (P < 0.05). There were significant decreases in vasodilatory response to endothelial-dependent vasodilator ADP after CP/CPB (P < 0.05). This alteration was more pronounced in UDM patients (P < 0.05). Conclusions: These data suggest that poorly controlled diabetes down-regulates endothelial adherens-junction protein activation/expression/localization in the setting of CP/CPB. The increased tyrosine phosphorylation and deterioration of VE-cadherin indicate the damage of the cell-cell endothelial junctions in the diabetic vessels undergoing CP/CPB and cardiac surgery. These alterations may lead to increase in vascular permeability and endothelial dysfunction and affect outcomes in diabetic patients after cardiac surgery.