Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function

Abstract

Aortic valve stenosis (AS) is a common heart valve disease in the elderly population, and its pathogenesis remains an interesting area of research. The degeneration of the aortic valve leaflets gradually progresses to valve sclerosis. The advanced phase is marked by the presence of extracellular fibrosis and calcification. Turbulent, accelerated blood flow generated by the stenotic valve causes excessive damage to the aortic wall. Elevated shear stress due to AS leads to the degradation of high-molecular weight multimers of von Willebrand factor, which may involve bleeding in the mucosal tissues. Conversely, elevated shear stress has been associated with the release of thrombin and the activation of platelets, even in individuals with acquired von Willebrand syndrome. Moreover, turbulent blood flow in the aorta may activate the endothelium and promote platelet adhesion and activation on the aortic valve surface. Platelets release a wide range of mediators, including lysophosphatidic acid, which have pro-osteogenic effects in AS. All of these interactions result in blood coagulation, fibrinolysis, and the hemostatic process. This review summarizes the current knowledge on high shear stress-induced hemostatic disorders, the influence of AS on platelets and antiplatelet therapy.

Keywords: antiplatelet therapy; aortic stenosis; cerebrovascular events; hemodynamics; platelets function; valvular heart disease; wall shear stress.

Figure 1

Hemodynamic models of aortic stenosis for (A) mild, (B) moderate, and (C) severe AS used in the experiment based on Juhn et al. [17]. Black arrow—direction of the stream flow, white arrows and numbers—diameter of the model expressed in centimeters.

Figure 2

Interaction between platelets and valvular interstitial cells in aortic valve stenosis. The black circle symbolizes a close-up on a cross-section through the aortic valve leaflet. Platelets adhere from the aortic side to the valve leaflets. Inside the circle, the left side shows a cross section through the aortic valve tissue with its layers, from the top: valve endothelial cells (pink flat), lamina fibrosa, lamina spongiosa, lamina ventricularis and in the middle valvular interstitial cells (pink spindle-shaped). The arrows symbolize the interaction between the different molecules. Ca²⁺—calcium ions.

Figure 3

Mechanism of platelet changes in aortic valve stenosis. PCT—plateletcrit; PDW—platelet distribution width; PLT—platelet. white arrow up—increase or intensification; white arrow down—decrease or reduction.