Abstract 18240: Fluid Shear Stress Regulates Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Through Mechanosensors in Endothelial Cells
Vascular endothelial cells (ECs), which form the innermost layer of blood vessels, are exposed to fluid shear stress that modulates endothelial function and vascular pathophysiology. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in endothelial dysfunction and progression of atherosclerosis. However, expression patterns and regulatory mechanisms in ECs under different fluid shear stress (FSS) have remained unclear. We demonstrated the expression pattern of LOX-1 by comparing the normal laminar shear stress (LSS), extremely high LSS and oscillatory shear stress (OSS). Confluent human umbilical vein endothelial cells (HUVECs) were exposed to a unidirectional steady flow for normal LSS (shear stress of 20 dyne/cm2) or extremely high LSS (shear stress of 120 dyne/cm2), and a bidirectional disturbed flow (shear stress of ± 5 dyne/cm2) for OSS, under various time periods. Western blot and RT-PCR analyses in ECs showed that OSS has upregulated LOX-1 expression in both protein and mRNA levels; on the other hand, LSS has downregulated them. Interestingly, extremely high LSS showed same patterns in LOX-1 expression, even though it is a unidirectional laminar flow. To identify the regulatory mechanisms of LOX-1 by FSS, HUVECs were transfected with siRNA of mechanosensors (VEGFR-2, VE-cadherin and PECAM-1) that are sensing the FSS patterns. Knockdown of these mechanosensors in ECs blocked OSS-induced upregulation of LOX-1 expression. These findings indicate that changes in pattern of FSS show different pattern on LOX-1 expression, and its regulation is mediated the mechanosensory complex in ECs.
Author Disclosures: J. Lee: None. J. Chung: None. K. Kim: None. S. An: None. K. Kwon: None.
- © 2016 by American Heart Association, Inc.