Associate Professor University of Central Florida, Florida, United States
Introduction: Cardiovascular disease (CVD) is one of many serious complications of diabetes. Prolonged periods of hyperglycemia can induce vascular changes resulting in endothelial dysfunction. Many studies have investigated the molecular mechanisms by which hyperglycemia affects the endothelium, however, few studies have looked at the mechanisms by which hyperglycemia can mechanically affect the structure and function of the endothelium. Additionally, studies investigating the effects of hyperglycemia on the endothelium utilize glucose concentrations that are not similar to the hyperglycemic values seen in people with diabetes.
Materials and
Methods: Human Umbilical Vein Endothelial Cells (HUVECs) were cultured in Medium 200 with Large Vessel Endothelial Supplement (LVES) containing either normoglycemia glucose (5.0 mM) or hyperglycemic glucose (13.9 mM) for 15 and 23 days. On days 15 and 23, the HUVECs were micropatterned on 1.2 kPa hydrogels. After 24 hours, traction force microscopy and monolayer stress microscopy was used to measure the tractions and intercellular stresses, respectively.
Results, Conclusions, and Discussions: After 15 days exposure, HUVECs cultured in hyperglycemic conditions exhibited decreased average normal intercellular stresses by 15.8%, increased maximum shear intercellular stresses by 5.6%, and increased RMS tractions by 59.9% compared to cells cultured in normoglycemic conditions. Additionally, after 23 days exposure, hyperglycemic conditions increased average normal intercellular stresses by 19.2%, increased average maximum shear intercellular stresses by 53.2%, and increased RMS tractions by 338.8% compared to cells cultured in normoglycemic conditions. Prolonged periods of hyperglycemia show both a decrease and increase in average normal intercellular stresses at 15 and 23 days, respectively, compared to endothelial cells cultured in normoglycemic conditions. At 15 and 23 days, the average maximum shear intercellular stresses and RMS tractions were increased compared to normoglycemic cultured cells. These results show that in addition to the molecular changes commonly seen in the endothelium after prolonged periods of hyperglycemia, there are also biomechanical changes occurring in the endothelial cells. Hyperglycemia can lead to many serious complications for people suffering from diabetes. While many studies have investigated the molecular changes occurring in the endothelium after exposure to hyperglycemic conditions, not much is known about the biomechanical changes in the endothelium after exposure to hyperglycemic conditions. Moreover, many studies investigating the effects of hyperglycemia on the endothelium use glucose concentrations that are not clinically relevant to the average hyperglycemic values seen in people with diabetes. Our study addresses this gap by using a glucose concentration that is clinically relevant and, as such, the results are potentially more realistic to the changes that would be observed in vivo. Future studies are needed to determine if the biomechanical response of HUVECs can be recovered after a return to a normoglycemic state.
