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      Shear Stress and Atherosclerosis

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          Abstract

          Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flow-dependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

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          Most cited references49

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          Endothelial cell functions.

          Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. Copyright 2003 Wiley-Liss, Inc.
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            Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis.

            Atherosclerosis is closely associated with disturbed flow characterized by low and oscillatory shear stress, but studies directly linking disturbed flow to atherogenesis is lacking. The major reason for this has been a lack of an animal model in which disturbed flow can be acutely induced and cause atherosclerosis. Here, we characterize partial carotid ligation as a model of disturbed flow with characteristics of low and oscillatory wall shear stress. We also describe a method of isolating intimal RNA in sufficient quantity from mouse carotid arteries. Using this model and method, we found that partial ligation causes upregulation of proatherogenic genes, downregulation of antiatherogenic genes, endothelial dysfunction, and rapid atherosclerosis in 2 wk in a p47(phox)-dependent manner and advanced lesions by 4 wk. We found that partial ligation results in endothelial dysfunction, rapid atherosclerosis, and advanced lesion development in a physiologically relevant model of disturbed flow. It also allows for easy and rapid intimal RNA isolation. This novel model and method could be used for genome-wide studies to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases.
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              SUMOylation and De-SUMOylation: wrestling with life's processes.

              The small ubiquitin-like modifier (SUMO) is a ubiquitin-like protein that covalently modifies a large number of cellular proteins. SUMO modification has emerged as an important regulatory mechanism for protein function and localization. SUMOylation is a dynamic process that is mediated by activating (E1), conjugating (E2), and ligating (E3) enzymes and readily reversed by a family of ubiquitin-like protein-specific proteases (Ulp) in yeast and sentrin/SUMO-specific proteases (SENP) in human. This review will focus on the de-SUMOylating enzymes with special attention to their biological function.
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                Author and article information

                Journal
                Mol Cells
                Mol. Cells
                ksmcb
                Molecules and Cells
                Korean Society for Molecular and Cellular Biology
                1016-8478
                0219-1032
                30 June 2014
                30 April 2014
                30 April 2014
                : 37
                : 6
                : 435-440
                Affiliations
                Aab Cardiovascular Research Institute, University of Rochester, Rochester, NY 14642, USA
                Author notes
                Article
                molcell-37-6-435
                10.14348/molcells.2014.0078
                4086336
                24781409
                4483deec-a25e-4331-8d52-8975f5f180c0
                ©The Korean Society for Molecular and Cellular Biology. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 03 April 2014
                : 07 April 2014
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