Fluid mechanical steady-state laminar wall shear stresses of 30 dyne/cm2 (high stress) and less than 1 dyne/cm2 (low stress) have been applied for varying times to confluent cultures of bovine aortic endothelial cells (BAECs) by means of two parallel plate channel flow chambers in series. BAEC cultures not exposed to shear or flow (no stress) were also studied. A shear stress of 30 dyne/cm2 resulted in cellular elongation and alignment, changes that were largely complete by 24 hr. In experiments in which BAECs were incubated with 125I-labeled low-density lipoprotein for 2 or 24 hr in the presence of shear stress levels, 125I-LDL internalization at 24 hr was increased (p < .05) in response to high-stress conditions. This increased uptake of 125I-LDL was observed in BAECs prealigned for 24 hr under high stress and in BAECs undergoing alignment in the presence of circulating 125I-LDL. BAECs were also exposed to shear stress for 24 hr in the presence of lipoprotein-deficient circulating medium to maximize LDL receptor expression. Receptor-mediated 125I-LDL internalization and degradation measured immediately after shear stress were both significantly enhanced (p < .01) in BAECs exposed to high stress. Furthermore, 125I-LDL binding studies at 4°C revealed a significant increase (p < .01) in specific 125I-LDL binding to BAECs exposed to high stress relative to those exposed to low or no stress. Nonspecific 125I-LDL endocytosis was not influenced by shear stress levels. High stress did not influence the incorporation of 3H-thymidine into BAEC DNA, indicating that the observed increase in LDL endocytosis was not dependent on an increase in cellular replication. The influence of high stress on LDL receptor expression and function suggests that the LDL receptor pathway is influenced by factors other than the cellular availability of exogenous cholesterol, in particular the recognition by BAECs of fluid mechanical signals and their transduction within the cell or on the cell surface. Our findings provide one potential mechanism through which hemodynamic shear stress might participate in cellular cholesterol homeostasis as well as atherogenesis.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)