Journal Article

Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells

Chakraborty, Amlan, Haribabu, Bodduluri, Chakraborty, Sutirtha, Sharp, M. Keith, Thomas, Jonathan M., Berson, R. Eric, Jala, Venkatakrishna R.

2016

Overview

This study demonstrated the effects of the directionality of oscillatory wall shear stress (WSS) on proliferation and proatherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of inflammatory mediators leukotriene B 4 (LTB 4 ) and bacterial lipopolysaccharide (LPS) from endothelial cells grown in an orbiting culture dish. Computational fluid dynamics (CFD) was applied to quantify the flow in the dish, while an analytical solution representing an extension of Stokes second problem was used for validation. Results indicated that WSS magnitude was relatively constant near the center of the dish and oscillated significantly (0–0.9 Pa) near the side walls. Experiments showed that LTB 4 dominated the shear effects on cell proliferation and area. Addition of LPS didn’t change proliferation, but significantly affected cell area. The expression of I-CAM1, E-Selectin and IL-6 were altered by directional oscillatory shear index (DOSI, a measure of the biaxiality of oscillatory shear), but not shear magnitude. The significance of DOSI was further reinforced by the strength of its interactions with other atherogenic factors. Hence, directionality of shear appears to be an important factor in regulating gene expression and provides a potential explanation of the propensity for increased vascular lesions in regions in the arteries with oscillating biaxial flow.

• Publisher: Springer US,Springer Nature B.V
• Subject: Atherosclerosis - metabolism / Atherosclerosis - pathology / Atherosclerosis - physiopathology / Bacteria / Biochemistry / Biological and Medical Physics / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Biomedicine / Biophysics / Bulging / Cell Proliferation - drug effects / Classical Mechanics / Computational fluid dynamics / E-Selectin - biosynthesis / Endothelial cells / Endothelial Cells - metabolism / Endothelial Cells - pathology / Fluid dynamics / Gene expression / Gene Expression Regulation / Humans / Hydrodynamics / Intercellular Adhesion Molecule-1 - biosynthesis / Interleukin-6 - biosynthesis / Leukotriene B4 - pharmacology / Lipopolysaccharides - toxicity / Mathematical models / Models, Cardiovascular / Shear / Shear Strength / Shear stress / Stokes law (fluid mechanics)