The impact of acute shear stress on venous endothelial cells inflammation and interaction with circulating white blood cells

Summary

The long saphenous vein is the most commonly used conduit in cardiac surgery; however, its use is complicated by high failure rates due to the development of vascular inflammation, intimal hyperplasia (IH) and accelerated atherosclerosis leading to grafts stenosis and occlusion. Inflammatory changes in vascular endothelial cells (EC) leading to the attachment of circulating white blood cells to the surface of the blood vessels (intima) then migrating to the inner part of the vessels (media) is a key step in activating the inner part smooth muscle cell (SMC) phenotype leading to SMC proliferation and migration to the luminal area of vessels (intima) which is the cornerstone in the development of IH and super-imposed atherosclerosis. Blood flow in vessels can exert a force on endothelial cells known as shear stress. Veins are usually subjected to low blood flow and shear stress in the body; however, when grafted into arterial circulation with high flow, they suddenly become exposed to high levels of shear stress. The impact of such acute changes in shear stress on ECs, interaction with circulating white blood cells and its role in the development of IH is not understood. Vascular EC can act as mechano-transducers which respond to flow changes by releasing mediators that regulate vascular inflammation and modulate circulating blood cells function and thereby IH . It has been shown that shear stress can induce vascular inflammation via signalling intermediaries in vein grafts due to the lack of anti-inflammatory regulators in venous EC. A greater understanding of the mechanisms underlying vein graft failure can reveal new therapies which may have major impact on patient's outcomes and health economics.