EFFECT OF GLYCATED SERUM ALBUMIN ON FUNCTIONAL MARKERS IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS IN THE PRESENCE OF SHEAR STRESS

Abstract

Regions of the vasculature subjected to low wall shear stress and disturbed flow patterns are prone to atherosclerotic plaque formation. Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance this risk. One of the contributory factors is the enhanced production of ROS by advanced glycation end products (AGE) of proteins and lipids formed in chronic diabetes. In this study, we examine the interaction of oscillatory wall shear stress and glycated serum albumin (AGE-HSA) in modulating NOsynthase activity and expression of pro-inflammatory molecules such as RAGE, s-ICAM-1 and matrix metalloproteinase (MMP-9) in cultured HUVEC. Our findings indicate that orbital shear stress (OSS) up-regulates RAGE expression at low (LSS 4.5 dyn/cm2) more than at high shear stress (HSS 12 dyn/cm2) at 4 h. This effect is promoted in the AGE-HSA (2 mg/mL) in a dose-dependent manner. Augmentation of NOsynthase activity was lower at LSS and further inhibited in the presence of AGE-HSA. Expression of s-ICAM-1 was found to be shear stress modulated with additive up-regulation in combination with AGE-HSA while MMP-9 was not affected by shear stress or AGE-HSA individually but in combination caused significant up-regulation. These changes in endothelial function correlate with mechanisms that initiate atherogenic process in diabetic macrovascular pathology.