title: Effects of diabetes and cardiopulmonary bypass on expression of adherens junction proteins in human peripheral tissue.
abstract: We investigated the changes in adherens junction proteins, such as vascular endothelial-cadherin and β-catenin, of skeletal muscle and vessels in patients with or without diabetes in the setting of cardiopulmonary bypass and cardiac operation.
  
  
  
  Skeletal muscle tissue samples were harvested pre- and post-cardiopulmonary bypass from nondiabetic (hemoglobin A1c: 5.4 ± 0.1), controlled diabetic (hemoglobin A1c: 6.3 ± 0.1), and uncontrolled diabetic patients (hemoglobin A1c: 9.6 ± 0.3) undergoing coronary artery bypass grafting operation (n = 8 per group). The expression/phosphorylation of adherens junction proteins vascular endothelial-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.
  
  
  
  The protein expression of total vascular endothelial-cadherin was not changed at baseline or between pre-and post-cardiopulmonary bypass among groups. The pre-cardiopulmonary bypass level of phospho-vascular endothelial-cadherin was found to be significantly increased in the uncontrolled diabetic patients group compared with the nondiabetic or controlled diabetic groups (P < .05). The post-cardiopulmonary bypass levels of phospho-vascular endothelial-cadherin were significantly increased compared with pre-cardiopulmonary bypass in all groups (P < .05 each), and this increase was greater in the uncontrolled diabetic patients group than that of the nondiabetic or controlled diabetic groups (P < .05). Expression of basal β-catenin protein in the uncontrolled diabetic group was decreased compared with nondiabetic or controlled diabetic groups (P < .05). There were significant decreases in the β-catenin protein expression between pre- and post-cardiopulmonary bypass in all 3 groups (P < .05 each), and this decrease was greater in the uncontrolled diabetic patients group than the nondiabetic group (P < .05). There were decreases in the relaxation response of skeletal muscle arterioles to substance P after cardiopulmonary bypass in all 3 groups (P < .05), and this alteration was more pronounced in the uncontrolled diabetic patients (P < .05).
  
  
  
  Uncontrolled diabetes causes inactivation and reduction in the expression of endothelial adherens junction proteins in the arterioles of skeletal muscle early after cardiopulmonary bypass. The enhanced phosphorylation of vascular endothelial-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.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Afshin
authors.initials: A
authors.lastname: Ehsan
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sellke
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Justin
authors.initials: J
authors.lastname: Liang
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address: fsellke@lifespan.org.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001160:Arterioles / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D048909:Diabetes Complications / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D006442:Glycated Hemoglobin; D051176:beta Catenin; D000099152:Cadherin 5