Mechanical stretch: physiological and pathological implications for human vascular endothelial cells - PubMed (original) (raw)

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

Nurul F Jufri et al. Vasc Cell. 2015.

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.

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Figures

Fig. 1

Fig. 1

Morphological change of human cerebral microvascular endothelial cells (HCMECs). The HCMECs were stained with Alexa 594 (red) for actin, and the nucleus was stained by DAPI (blue). a HCMECs that were not exposed to stretch were rounded in shape. b HCMECs that were exposed to 18 h cyclic stretch became elongated in shape

Fig. 2

Fig. 2

Pathological consequences of altered mechanical stretch. Pathological stretch could change the hemodynamic properties of blood flow in the vascular system. The excessive strain causes cell deformation and the endothelial cell response activates biochemical signaling. Vascular adaptation through remodeling results in ECM synthesis and degradation, proliferation and apoptosis to maintain the vascular physiological state. However, persistent pathological mechanical stretch due to hypertension triggers endothelial dysfunction, pro-inflammatory responses, neointima formation, structural alteration, ROS formation and arterial stiffening. These result in the formation of vascular anomalies such as atherosclerosis, restenosis and aneurysms

Fig. 3

Fig. 3

Summary of the mechanisms involved in human cerebral microvascular endothelial cells induced by mechanical stretching. Stretch stimuli are sensed by mechanoreceptors of the endothelial cell that transduce downstream protein signals. This will result in gene activation and increased protein synthesis that alters cell phenotype and function. However, different stretch intensity, magnitude and duration may activate different mechanisms. Physiological stretch is beneficial in maintaining healthy blood vessels; however, pathological stretch, as is observed in hypertension, could activate pathways leading to disease development. Thus, it is important to understand and elucidate the signaling involved with these processes as this could aid in the identification of novel therapeutic approaches aimed at treating vascular related diseases. Ca 2+ Calcium ion, ECM Extracellular matrix, EDHF Endothelium derived hyperpolarizing factor, EET Epoxyeicosatrienoic acid, eNOS Endothelial nitric oxide synthase, ET-1 Endothelin 1, MCP-1 Monocyte chemoattractant protein-1, NO Nitric oxide, PECAM-1 Platelet endothelial cell adhesion molecule 1, ROS Reactive oxygen species, SA channel Stretch activated channel, TK receptors Tyrosine kinase receptors, VCAM-1 Vascular cell adhesion molecule-1, VE-cadherin Vascular endothelial cadherin, wPB Weibel-Palade Bodies

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