Journal ArticleDOI
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Eleni Tzima,Mohamad Irani-Tehrani,William B. Kiosses,Elizabetta Dejana,David A. Schultz,Britta Engelhardt,Gaoyuan Cao,Horace M. DeLisser,Martin A. Schwartz,Martin A. Schwartz +9 more
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TLDR
In this paper, the authors investigated the pathway upstream of integrin activation and found that PECAM-1 and VEGFR2 are sufficient to confer responsiveness to flow in heterologous cells.Abstract:
Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-kappaB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.read more
Citations
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VEGF receptor signalling - in control of vascular function.
TL;DR: Recent insights have shed light onto VEGFR signal transduction and the interplay between different V EGFRs and VEGF co-receptors in development, adult physiology and disease.
Journal ArticleDOI
Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives
Jeng Jiann Chiu,Shu Chien +1 more
TL;DR: Current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications are summarized to contribute to the understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
Journal ArticleDOI
Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus
TL;DR: The molecular mechanisms by which forces might act at a distance to induce mechanochemical conversion in the nucleus and alter gene activities are explored.
Journal ArticleDOI
Cellular mechanotransduction: putting all the pieces together again.
TL;DR: Future research in this area will require analysis, understanding, and modeling of tensionally integrated systems of mechanochemical control, and the presence of isometric tension at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response.
Journal ArticleDOI
Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.
Yiannis S. Chatzizisis,Ahmet U. Coskun,Michael Jonas,Elazer R. Edelman,Elazer R. Edelman,Charles L. Feldman,Peter Stone +6 more
TL;DR: The molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling are explored and likely mechanisms concerning the different natural history trajectories of individual coronary lesions are indicated.
References
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Journal ArticleDOI
Upregulation of VCAM-1 and ICAM-1 at Atherosclerosis-Prone Sites on the Endothelium in the ApoE-Deficient Mouse
TL;DR: The levels, localization, and characteristics of expression of VCAM-1, ICAM-2, and PECam-1 appear to be differentially regulated, and upregulation of VC AM-1 and ICAM -1 is associated with sites of lesion formation.
Journal ArticleDOI
The Elongation and Orientation of Cultured Endothelial Cells in Response to Shear Stress
M. J. Levesque,Robert M. Nerem +1 more
TL;DR: The results show that endothelial cells orient with the flow direction under the influence of shear stress, the time required for cell alignment with flow direction is somewhat longer than that needed for cell elongation, and there is a strong correlation between the degree of alignment and endothelial cell shape.
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The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation.
TL;DR: Preferential regional activation of endothelial NF-kappaB by systemic stimuli, including hypercholesterolemia, may contribute to the localization of atherosclerotic lesions at sites with high steady-state expression levels of NF- kappaB/Ikappa B components.
Journal ArticleDOI
Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment.
TL;DR: The role of integrins and Rho are defined in a pathway leading to endothelial cell adaptation to flow by shear stress rapidly stimulates conformational activation of integrin αvβ3 in bovine aortic endothelial cells, followed by an increase in its binding to extracellular cell matrix (ECM) proteins.
Journal ArticleDOI
Mechanotransduction in Response to Shear Stress ROLES OF RECEPTOR TYROSINE KINASES, INTEGRINS, AND Shc
TL;DR: The results indicate that receptor tyrosine kinases and integrins can serve as mechanosensors to transduce mechanical stimuli into chemical signals via their association with Shc.
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