Mechanical stretch: physiological and pathological implications for human vascular endothelial cells

Abstract

Vascular endothelial cells are subjected to hemodynamic forces such as mechanical stretch due to the pulsatile nature of blood flow. Mechanical stretch of different intensities is detected by mechanoreceptors on the cell surface which enables the conversion of external mechanical stimuli to biochemical signals in the cell, activating downstream signaling pathways. This activation may vary depending on whether the cell is exposed to physiological or pathological stretch intensities. Substantial stretch associated with normal physiological functioning is important in maintaining vascular homeostasis as it is involved in the regulation of cell structure, vascular angiogenesis, proliferation and control of vascular tone. However, the elevated pressure that occurs with hypertension exposes cells to excessive mechanical load, and this may lead to pathological consequences through the formation of reactive oxygen species, inflammation and/or apoptosis. These processes are activated by downstream signaling through various pathways that determine the fate of cells. Identification of the proteins involved in these processes may help elucidate novel mechanisms involved in vascular disease associated with pathological mechanical stretch and could provide new insight into therapeutic strategies aimed at countering the mechanisms’ negative effects.

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

“…Thus, these water/D 2 O CARS images reflect the location of pressure gradients across the artery wall at subcellular resolution. Consequently, the high permeability of the EAM coupled to the low permeability of the EBM results in a very efficient transfer of the arterial pressure to the immediately adjacent elastin and collagen macromolecule infrastructure without generating stress on the mechanically sensitive EC (30,31). It is important to note that the low water compressibility [6 × 10 −4 % volume change/100 mmHg (32)] results in very little water movement to equilibrate the arterial pressure with the endothelium cytosol.…”

A vacuum-actuated microtissue stretcher for long-term exposure to oscillatory strain within a 3D matrix

“…The average (n=9) peak dynamic bulk strain was directly related to the applied vacuum with some nonlinearity at higher pressures (figure 3c). At 90kPa, the peak strain was 13.0 ± 0.9(SD)%, which covers the physiological range, [19][20][21][22] and was highly reproducible.…”

“…[19][20][21][22] For two reasons it is critical to continue this work using 3D cell culture. First, a third dimension for cell adhesion significantly affects integrin/adhesion distribution and the cytoskeletal structure, 6 which may alter how mechanical inputs are perceived.…”

“…Although higher strain may be achievable through increased vacuum pressure or further optimizing device dimensions and materials, this strain sufficiently covers the physiological range in airways and blood vessels and is a sufficient stimulus to produce measurable differences in cell behavior. [19][20][21][22] In this paper, we provided proof of concept for a device to stretch an array of lab grown microtissues consisting of fibroblasts and a reconstituted collagen matrix. Although this is a significant step forward in terms of physiological relevance compared to 2D cell culture, much is still needed to fully recapitulate the in vivo environment on a chip.…”

Engineering Approaches for Creating Skeletal Muscle

“…67 Some researchers suggest that this perpendicular orientation reduces the strain on the cells. 68 Stretching the collagen gel on which the BAECs were cultured was enough to increase the number of vascular sprouts into the gel as much as vascular endothelial growth factor (VEGF) treatment. 67 This response was determined to occur through Rho-associated protein kinase (ROCK)-dependent pathways.…”