Department of Infection, Immunity and Cardiovascular Disease, the INSIGNEO Institute for In Silico Medicine and the Bateson Centre, University of Sheffield, England, UK.
Published: June 2017
AI Article Synopsis
Article Abstract
Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.
Damage models have significantly advanced predictions of ductile fractures in large, thin-walled structures like automobiles, ships, and aircraft. However, accurately predicting these fractures remains challenging due to variations in strain localization, ranging from biaxial compression to tension. This study introduces a specialized damage model for shell elements, utilizing data from shear, uniaxial, and plane tension tests.
The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation.
Background And Objective: Deep vein thrombosis (DVT) of the lower limbs is a critical global vascular disease. Accurately assessing and predicting the efficacy of DVT treatment remains a significant challenge due to a lack of understanding of the mechanisms by which the level of patient-specific embolization and the rate of drug injection affect thrombolytic therapy.
Methods: In this study, we used the computed tomographic venography (CTV) clinical method to obtain patient-specific parameters, and the flow-solid interaction (FSI) method combined with biochemical response modeling of thrombolysis to analyze patient-specific hemodynamic and biomechanical characteristics and to quantitatively assess the effects of three vessel embolism levels (VEL) versus two drug injection rates (DIR) on bifurcated femoral venous thrombolytic therapy.
The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China; Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China;; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China. Electronic address:
In the circulatory system, the microenvironment surrounding cancer cells is complex and involves multiple coupled factors. We selected two core physical factors, shear stress and hydraulic resistance, and constructed a microfluidic device with dual negative inputs to study the trade-off movement behavior of cancer cells when facing coupled factors. We detected significant shear stress escape phenomena in the MDA-MB-231 cell line and qualitatively explained this behavior using a cellular force model.
