Low or oscillatory shear stress and endothelial permeability in atherosclerosis

Abstract

Endothelial shear stress is a tangential stress derived from the friction of the flowing blood on the endothelial surface of the arterial wall and is expressed in units of force/unit area (dyne/cm²). Branches and bends of arteries are exposed to complex blood flow patterns that generate low or oscillatory endothelial shear stress, which impairs glycocalyx integrity, cytoskeleton arrangement and endothelial junctions (adherens junctions, tight junctions, gap junctions), thus increasing endothelial permeability. The lipoproteins and inflammatory cells penetrating intima due to the increased endothelial permeability characterizes the pathological changes in early stage of atherosclerosis. Endothelial cells are critical sensors of shear stress, however, the mechanisms by which the complex shear stress regulate endothelial permeability in atherosclerosis remain unclear. In this review, we focus on the molecular mechanisms of the endothelial permeability induced by low or oscillatory shear stress, which will shed a novel sight in early stage of atherosclerosis.

Keywords: atherosclerosis; cytoskeleton arrangement; endothelial junctions; endothelial permeability; glycocalyx; shear stress.

FIGURE 1

Endothelial integrity and increased endothelial permeability. Low or oscillatory shear stress impairs glycocalyx integrity, thus increasing endothelial permeability. Inflammatory cells and LDL infiltrate into intima due to increased endothelial permeability, which causes progression of atherosclerosis.

FIGURE 2

Endothelial integrity and increased endothelial permeability. Low or oscillatory shear stress impairs cell-cell junctions and cytoskeletal arrangement, thus increasing endothelial permeability. The injured cell-cell junctions include adherens junctions (VE-cadherin binds to p120-catenin, β-catenin or plakoglobin), tight junctions (occludin, claudin and ZO) and gap junctions (Cx37, Cx40 and Cx43).

FIGURE 3

The mechanisms of low or oscillatory shear stress on increased endothelial permeability by impairing glycocalyx integrity, cytoskeletal arrangement and cell-cell junctions (such as, adherens junctions, tight junctions and gap junctions). 1) Low or oscillatory shear stress increases endothelial permeability by regulating core proteins of glycocalyx and key elements of cytoskeleton and cell-cell junctions (adherens junctions and tight junctions). 2) Low or oscillatory shear stress increases endothelial permeability by regulating PAK/NF-κB signaling, RhoA signaling, JNK signaling pathways and so on.