Influence of a laminar steady-state fluid-imposed wall shear stress on the binding, internalization, and degradation of low-density lipoproteins by cultured arterial endothelium

Abstract

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 less than .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 a 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 less than .01) in BAECs exposed to high stress. Furthermore, 125I-LDL binding studies at 4 degrees C revealed a significant increase (p less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)