Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-α and monocytic cell recruitment in a simplified model of arterial bifurcations

• Published in: Atherosclerosis Vol. 207; no. 1; pp. 93 - 102
• Main Authors: Cicha, Iwona, Beronov, Kamen, Ramirez, Efrain Lopez, Osterode, Katharina, Goppelt-Struebe, Margarete, Raaz, Dorette, Yilmaz, Atilla, Daniel, Werner G, Garlichs, Christoph D
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.11.2009; Elsevier
• Subjects: Anti-Inflammatory Agents - pharmacology; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - immunology; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cardiovascular; Cell Adhesion - drug effects; Cell Culture Techniques; Cells, Cultured; Computer Simulation; E-Selectin - metabolism; Endothelial Cells - drug effects; Endothelial Cells - immunology; Endothelium; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Models, Cardiovascular; Monocytes - drug effects; Monocytes - immunology; Monocytic cell adhesion; NF-kappa B - metabolism; Numerical Analysis, Computer-Assisted; Resveratrol; Shear stress; Simvastatin - pharmacology; Statins; Stilbenes - pharmacology; Stress, Mechanical; Stress, Physiological; Time Factors; Tumor Necrosis Factor-alpha - immunology; Vascular Cell Adhesion Molecule-1 - metabolism; Vertebrates: cardiovascular system; Shear stress; Monocytic cell adhesion; Statins; Atherosclerosis; Resveratrol; Endothelium; Cytokine; Cardiovascular disease; Statin derivative; Antioxidant; Stilbene derivatives; Vascular disease; Preconditioning; Tumor necrosis factor α; Antilipemic agent
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.04.034

Abstract Objective Atherosclerotic plaque formation results from a combination of local shear stress patterns and inflammatory processes. This study investigated the endothelial response to shear stress in combination with the inflammatory cytokine TNF-α in a simplified model of arterial bifurcation. Methods Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by stimulation with TNF-α. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Endothelial protein expression was determined by immunofluorescence. Results Adhesion of monocytic cells to unstimulated ECs was nearly undetectable under laminar shear stress and was slightly increased under non-uniform shear stress. Exposure of ECs to non-uniform shear stress in combination with TNF-α induced a 12-fold increase in monocytic cell recruitment and a significant induction of endothelial E-selectin and VCAM-1 expression. Both these effects were prevented in ECs exposed to laminar shear stress. The significant differences in TNF-α-induced monocytic cell recruitment and adhesion molecule expression between laminar and non-uniform shear stress regions were abolished in the absence of shear stress preconditioning. Simvastatin (1 μmol/L) suppressed the non-uniform shear stress- and TNF-α-induced increase in monocytic cell adhesion by about 30% via inhibition of VCAM-1 expression. Resveratrol, the active component of red wine, inhibited the expression of both VCAM-1 and E-selectin, and reduced monocytic cell recruitment by 50% at 20 μmol/L. Conclusions Non-uniform shear stress induces endothelial susceptibility to circulating TNF-α and adhesion of monocytic cells. Interference with this process may inhibit inflammatory response in atherosclerosis-prone regions.