Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature

Figures

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  Figure 1. Structure of the arterial wall. The endothelial cells are in direct contact with blood flow in the intimal layer, while smooth muscle cells lie within the tunica media layer. Image was created from Servier Medical Art Commons (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

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  Figure 2. Aortic valve leaflet consisting of fibrosa, spongiosa, and ventricularis layers (12), which contain valve endothelial cells (VEC) on the surfaces and valve interstitial cells (VIC) deep within the tissues. The fibrosa layer is enriched with collagen, while the spongiosa layer mainly consists of glycosaminoglycans (GAGs) and the ventricularis has a high concentration of elastin fibers (11). Flow on the ventricularis side induces laminar shear stress, while the fibrosa side experiences oscillatory shear stress. The fibrosa side which is dominated by relatively lower shear stresses and disturbed, oscillatory flow patterns is a common site for calcified nodules in the manifestation of calcific aortic valve disease (CAVD). Figure reproduced with permission from Ohukainen P, Ruskoaho H & Rysa J. Cellular Mechanisms of Valvular Thickening in Early and intermediate Calcific Aortic Valve Disease. Current Cardiology Reviews 2018 14 264–271. Published by Bentham Science (12).

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  Figure 3. Closed healthy tricuspid aortic valve (A) and calcified tricuspid aortic valve (B). Calcified valves cannot open or close properly due to hardened leaflets from calcium deposition. These calcium nodules prevent the leaflet from movement or deformation. The cell types involved in pathological changes are primarily VECs and VICs; however, their specific pathological mechanisms remain unclear. Image was created from Servier Medical Art Commons (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

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  Figure 4. The cardiac jelly consists of an extracellular matrix which separates the outer myocardium layer from the inner endothelium layer. During valve formation, a small portion of the endocardial endothelial cells delaminate, differentiate, and migrate into the cardiac jelly, where they repopulate and differentiate to remodel valve tissues. Oscillatory flow-sensitive genes include WNT, NOTCH, BMP, and VEGF, which are essential components in various stages of cardiac development. Figure reproduced with permission from Armstrong EJ & Bischoff J. Heart valve development: endothelial cell signaling and differentiation. Circulation Research 2004 95 459–470. Published by American heart Association (27).

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  Figure 5. Regions of oscillatory blood flow in valve vs in blood vessel bifurcations. (A and B) Illustrate oscillatory flow on the leaflet’s fibrosa side and the distribution of flexural compression (fibrosa) and tensile stresses (ventricularis) during valve open and closed states, respectively. (C) Depicts a straight segment of vasculature that experiences laminar flow. Oscillatory flow is formed at bifurcation sites downstream of the straight segment. It is observed that regions of flow oscillations are most vulnerable to plaque formation or calcification (76, 77).