The effect of salvianolic acid B combined with laminar shear stress on TNF-α-stimulated adhesion molecule expression in human aortic endothelial cells

Abstract

The study was conducted to investigate the effect of Salvianolic acid B (Sal B) on TNF-alpha-stimulated adhesion molecule expression i.e. vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human aortic endothelial cells (HAECs) under laminar shear stress (LSS) condition. Exposure of HAECs to LSS (12 dynes/cm(2) for 6 h decreased the TNF-alpha-induced protein expression of adhesion molecules i.e. VCAM-1, ICAM-1 and E-selectin. Pre-treatment of HAECs with Sal B (10 microg/ml) then exposed to LSS (12 dynes/cm(2)) for 6 h significantly inhibited VCAM-1, ICAM-1 and E-selectin expression stimulated by TNF-alpha. Moreover, combined Sal B and LSS treatment inhibited the adhesiveness of monocytic U937 cells to TNF-alpha-stimulated HAECs. We further examined the molecular mechanisms and found that the combination of Sal B and LSS treatment dramatically inhibited TNF-alpha-induced NF-kappaB activation evidenced by IkappaBalpha degradation and p65 nuclear translocation in HAECs. This study provides the first biomechanopharmacological evidence that Sal B has a combination effect with LSS to reduce the expression of three adhesion molecules, leading to reduced monocyte adhesion to HAECs, at least in part, by inhibiting the NF-kappaB signaling pathway. Data from this study thus support the potential clinical application of Sal B in vascular inflammatory diseases.