Abstract 18936: Fluid Shear Stress Regulates Expression of Coxsackievirus-adenovirus Receptor Through Mechanosensory Complex in Endothelial Cells
Backgrounds: Vascular endothelial cells, which form the innermost layer of blood vessels, are exposed to fluid shear stress that modulates endothelial function and vascular pathophysiology. The coxsackie- and adenovirus receptor (CAR) is a transmembrane protein belonging to the immunoglobulin superfamily. However, the function of CAR as a virus receptor has been extensively studied, while its physiological role and expression pattern in endothelial cells under fluid shear stress have remained less clear.
Methods and Results: We demonstrated that mechanisms involved in CAR expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells. Confluent HUVECs were exposed to a unidirectional steady flow (shear stress of 25 dyne/cm2) for laminar shear stress (LSS), and a bidirectional disturbed flow (shear stress of ± 5 dyne/cm2) for oscillatory shear stress (OSS), under various time periods. Additionally, we used a model of atherosclerosis induced by disturbed flow in mice by partial carotid artery ligation. Western blot and RT-PCR analyses in HUVECs showed that OSS has upregulated CAR expression in both protein and mRNA levels; on the other hand, LSS has downregulated them. In enface staining of mice with partial carotid artery ligation, ligated left carotid artery (LCA) with OSS showed significantly increased CAR expression compared to expression from normal right carotid artery (RCA). In knockdown of CAR in HUVECs with siRNA encoding CAR, suppression in phosphorylation of Akt and eNOS by OSS was improved, whereas LSS-induced phosphorylation of Akt and eNOS was much activated. Moreover, transfection of HUVECs with siRNA encoding VEGFR2, PECAM-1 and VE-cadherin blocked OSS-induced CAR expression.
Conclusions: Our results indicate that fluid shear stress can regulate CAR expression in endothelial cells and its regulation is mediated through the mechanosensory complex. Furthermore, it suggests that inhibition of CAR expression may lead to protective effects in endothelial cells via improving stimulation in signaling of mechanosensor under fluid shear stress. (Acknowledgements: NRF-2011-0019695)
Author Disclosures: J. Chung: None. G. Lee: None. K. Kim: None. Y. Lee: None. S. Lee: None. S. An: None. K. Kwon: None.
- © 2015 by American Heart Association, Inc.