Shear type and magnitude affect aortic valve endothelial cell morphology, orientation, and differentiation

Abstract

Valvular endothelial cells line the outer layer of heart valves and can withstand shear forces caused by blood flow. In contrast to vascular endothelial cells, there is limited amount of research over valvular endothelial cells. For this reason, the exact physiologic behavior of valvular endothelial cells is unclear. Prior studies have concluded that valvular endothelial cells align perpendicularly to the direction of blood flow, while vascular endothelial cells align parallel to blood flow. Other studies have suggested that different ranges of shear stress uniquely impact the behavior of valvular endothelial cells. The goal of this study was to characterize the response of valvular endothelial cell under different types, magnitudes, and durations of shear stress. In this work, the results demonstrated that with increased shear rate and duration of exposure, valvular endothelial cells no longer possessed the traditional cuboidal morphology. Instead through the change in cell circularity and aspect ratio, valvular endothelial cells aligned in an organized manner. In addition, different forms of shear exposure caused the area and circularity of valvular endothelial cells to decrease while inducing mesenchymal transformation validated through αSMA and TGFβ1 expression. This is the first investigation showing that valvular endothelial cells alignment is not as straightforward as once thought (perpendicular to flow). Different types and magnitudes of shear induce different local behaviors. This is also the first demonstration of valvular endothelial cells undergoing EndMT without chemical inducers on a soft surface in vitro. Findings from this study provide insights to understanding the pathophysiology of valvular endothelial cells which can potentially propel future artificial engineered heart valves.

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks

“…Compare these results to a study by Kang et al, which showed that shear stress of 3–5.3 dyne/cm 2 stimulated sprout formation by cells cultured in three dimensions and that 12 dyne/cm 2 inhibited growth 13 . Shear stress values used to study endothelial cell responses range from 0.1 to 50 dyne/cm 2 14–16 . Even studies using 100 dyne/cm 2 17 can be found.…”

“…13 Shear stress values used to study endothelial cell responses range from 0.1 to 50 dyne/cm 2 . [14][15][16] Even studies using 100 dyne/cm 217 can be found. The range in shear stresses used for in vitro studies and the variable responses provoke additional questions about the physiological relevance of the assays.…”

Polarity-JaM: An image analysis toolbox for cell polarity, junction and morphology quantification

“…(16) demonstrated that cell size is modulated by shear flow. Longer exposure to shear flow decreases cell area, while increasing cell aspect ratio across longer (approx.…”

“…As shear stress increases, endothelial cells polarise against flow, however, this phenotype is ablated with EC senescence. In addition, Deb et al (14) demonstrated that cell size is modulated by shear flow. Longer exposure to shear flow decreases cell area, while increasing cell aspect ratio across longer (approx.…”

“…Collective cellular orientation has also been correlated with both shear flow types, pulsatile and laminar, which have been shown to organise collective EC phenotypes. Pulsatile flow does not organise the direction of orientation as strongly as laminar flow (16, 17).…”