Abstract 17960: Differential Impairment of Adherence-Junction Expression/Phosphorylation of Human Myocardium in the Setting of Diabetes After Cardioplegia
Background: Previous experimental and clinical studies have demonstrated that endothelial adherence-junction molecules are significantly altered in the animal and human myocardium and microvasculature after cardioplegia and cardiopulmonary bypass (CP/CPB). We investigated the effects of diabetes on expression/phosphorylation of VE-cadherin, β- and γ-catenin in the atrial myocardium in the setting of CP/CPB.
Methods: Right atrial tissue was harvested pre- and post-CP/CPB from controlled (CDM) and uncontrolled diabetic (UDM) and non-diabetic (ND) patients (n = 6 - 8/group). Expressions/phosphorylation/localization of VE-cadherin, β-catenin and γ-catenin were assessed by immuno-blotting and immuno-precipatation. Arteriolar endothelial function was assessed by videomicroscopy in response to the endothelium-dependent vasodilator ADP.
Results: There were no significant differences in basal protein expression of VE-cadherin between UDM and CDM or ND patients. There were no significant differences in VE-cadherin expression between pre- and post-CP/CPB among groups. The level of basal phosphorylated VE-cadherin tends to be 61% higher in the UDM group compared with ND (P = 0.007). CP/CPB induced more phosphorylation of VE-cadherin in all groups (60% in ND; 57% in CDM and 65% vs. pre-CP/CPB; P<0.05, respectively) and this effect was more pronounced in the UDM group (P < 0.05 vs. ND or CDM). The protein levels of both catenins (β and γ) were lower in post-CP/CPB in UDM patients than ND (P<0.05). There were significantly decreases in vasodilatory response to endothelial-dependent vasodilator ADP after CP/CPB (P<0.05). This alteration was more pronounced in the UDM patients (P<0.05).
Conclusion: These data suggest that poorly controlled diabetes down-regulates endothelial adherence-junction protein activation/expression in the setting of CP/CPB. The increased tyrosine phosphorylation and deterioration of VE-cadherin indicates the damage of the cell-cell endothelial junctions in the diabetic vessels undergoing CP/CPB and cardiac surgery. These alterations may lead to the increase in vascular permeability and endothelial dysfunction and affect outcomes in diabetic patients after cardiac surgery.
- © 2013 by American Heart Association, Inc.