Nuclear mechanosensing of the aortic endothelium in health and disease

Disease Models & Mechanisms, Год журнала: 2023, Номер 16(10)

Опубликована: Окт. 1, 2023

ABSTRACT The endothelium, the monolayer of endothelial cells that line blood vessels, is exposed to a number mechanical forces, including frictional shear flow, pulsatile stretching and changes in stiffness influenced by extracellular matrix composition. These forces are sensed mechanosensors facilitate their transduction drive appropriate adaptation endothelium maintain vascular homeostasis. In aorta, unique architecture vessel gives rise fluid dynamics, which, turn, shape cellular morphology, nuclear architecture, chromatin dynamics gene regulation. this Review, we discuss recent work focusing on how differential exerted transduced influence form function giving spatial variation aorta. We will also developments understanding mechanosensing implicated diseases

Язык: Английский

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Silk fibroin promotes H3K9me3 expression and chromatin reorganization to regulate endothelial cell proliferation

APL Bioengineering, Год журнала: 2024, Номер 8(2)

Опубликована: Май 29, 2024

Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing regeneration, has not been thoroughly investigated its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels SF-treated EC, as evidenced by immunofluorescence western blot analysis. The H2B-eGFP demonstrate that SF treatment results accumulation H2B-marked chromatin nuclear inner cavities EC. Inhibition a deacetylase inhibitor TSA decreased cell proliferation. Furthermore, MAPK signaling pathway using chromium picolinate proliferative activity level also appeared enhance growth proliferation modulating reorganizing chromatin, particularly after oxidative stress induced H

Язык: Английский

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Histone modification of endothelial-mesenchymal transition in cardiovascular diseases

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Дек. 7, 2022

Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like characteristics, contributes to the formation development of atherosclerotic plaques. Until now, there still lack effective measures treat atherosclerosis (AS), so an urgent need understand underlying mechanisms AS. In addition, although various studies have shown that EndMT involved pathological stages cardiovascular diseases, such as myocardial fibrosis, hypertrophy, hypertension, specific molecular driving are exploratory stage. this review, we review role histone modifications (methylation, demethylation acetylation, deacetylation) on disease, aiming target histone-modifying enzymes guide disease therapy.

Язык: Английский

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Controlled disturbed flows on the endothelium result in increased inflammation, nuclear lamin disruption and heterochromatin condensation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 28, 2023

Abstract Early atherosclerotic lesions often develop in areas of disturbed flow within arterial curvatures and bifurcations. Complex flows alter the signaling inflammatory other molecules that may exacerbate disease phenotype. Microfluidic platforms to assess changes endothelial mechanobiology generally employ laminar unidirectional or oscillatory generated straight channels; such do not however mimic complex time-varying bi-directional shear patterns on walls. We fabricated an endothelium-on-chip device generate “controlled” flows, characterized using a wall rosette, as those reported aneurysmal vessels regions with plaques. cultured human aortic cells (HAEC) subjected monolayer circular rosette which represents bidirectional stresses. Immunofluorescence results show large cuboidal significantly higher nuclear areas, localization VE-Cadherin, elevated actin NF-kB expressions compared cell monolayers flow, No-flow conditions. The creation dysfunctional due also correlated dramatic lamin A/C distribution heterochromatin organization nucleus have been earlier. Such studies are potentially useful novel therapeutics, mitigate effects vascular for personalized medicine, study thrombus vicinity inflamed monolayers, reduce ourreliance animal trials. Our analytical method represent first successful demonstration generating controlled microfluidic devices

Язык: Английский

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Disrupted stiffness ratio alters nuclear mechanosensing

Matter, Год журнала: 2023, Номер 6(10), С. 3608 - 3630

Опубликована: Сен. 1, 2023

Язык: Английский

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Mechanotransduction of the vasculature in Hutchinson-Gilford Progeria Syndrome

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Авг. 22, 2024

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder that causes severe cardiovascular disease, resulting in the death of patients their teenage years. The disease pathology caused by accumulation progerin, mutated form nuclear lamina protein, lamin A. Progerin binds to inner membrane, disrupting integrity, and abnormalities changes gene expression. This results increased cellular inflammation, senescence, overall dysfunction. molecular mechanisms which progerin induces are not fully understood. Progerin’s detrimental impact on mechanics role nucleus as mechanosensor suggests dysfunctional mechanotransduction could play HGPS. especially relevant cells exposed dynamic, continuous mechanical stimuli, like those vasculature. endothelial (ECs) smooth muscle (SMCs) within arteries rely physical forces produced blood flow maintain function homeostasis. Certain regions produce disturbed flow, leading an impaired transduction signals, reduction function, also occurs In this review, we discuss mechanotransduction, how disrupted HGPS, what effect has cell health function. We address healthy responses ECs SMCs physiological stimuli these accumulation.

Язык: Английский

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Behavior of a Confluent Layer of Myoblasts Under Shear Flow

Journal of Engineering and Science in Medical Diagnostics and Therapy, Год журнала: 2023, Номер 7(1)

Опубликована: Июнь 10, 2023

Abstract To investigate the effect of shear stress direction on cell activity in a confluent layer, migration and deformation cells oriented parallel or perpendicular to flow field were optically tracked vitro. A Couette-type between walls was formed lower stationary culture dish upper rotating disk. Shear (<2 Pa) set by adjusting rotational speed Myoblasts (C2C12: mouse myoblast line) cultured an incubator equipped with inverted phase-contrast microscope under continuous for 7 days until confluency. Deformation each time-lapse images. Analysis these images showed that deform migrate along their major axis even at confluency (whether is field). As result, orientation remains field. This observation may be used improve development engineered muscle tissue.

Язык: Английский

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