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      Model-based vascular elastography improves the detection of flow-induced carotid artery remodeling in mice

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          Abstract

          Increased arterial thickness measured with ultrasound correlates with future cardiovascular events, but conventional ultrasound imaging techniques cannot distinguish between intima, media, or atherosclerotic plaque in the carotid artery. In this work, we evaluated how well vascular elastography can detect intimal changes in a mouse model of carotid remodeling. We ligated the left external and internal branches of the carotid artery of male FVB mice and performed sham operations for 2 weeks. High-resolution ultrasound imaging accurately detected lower blood velocities and low blood volume flow in the carotid arteries after ligation in FVB mice. However, ultrasound could not detect differences in the carotid wall even at 2 weeks post-surgery. The Young’s modulus was measured based on displacements of the carotid artery wall, and Young’s modulus was 2-fold greater in shams at 1 week post ligation, and 3-fold greater 2 weeks after ligation. Finally, the higher Young’s modulus was most associated with higher intimal thickness but not medial or adventitial thickness as measured by histology. In conclusion, we developed a robust ultrasound-based elastography method for early detection of intimal changes in small animals.

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          Most cited references47

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          Elastography: A Quantitative Method for Imaging the Elasticity of Biological Tissues

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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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              Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling.

              The vascular endothelium mediates the ability of blood vessels to alter their architecture in response to hemodynamic changes; however, the specific endothelial-derived factors that are responsible for vascular remodeling are poorly understood. Here we show that endothelial-derived nitric oxide (NO) is a major endothelial-derived mediator controlling vascular remodeling. In response to external carotid artery ligation, mice with targeted disruption of the endothelial nitric oxide synthase gene (eNOS) did not remodel their ipsilateral common carotid arteries whereas wild-type mice did. Rather, the eNOS mutant mice displayed a paradoxical increase in wall thickness accompanied by a hyperplastic response of the arterial wall. These findings demonstrate a critical role for endogenous NO as a negative regulator of vascular smooth muscle proliferation in response to a remodeling stimulus. Furthermore, our data suggests that a primary defect in the NOS/NO pathway can promote abnormal remodeling and may facilitate pathological changes in vessel wall morphology associated with complex diseases such as hypertension and atherosclerosis.
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                Author and article information

                Contributors
                Slava_Korshunov@URMC.rochester.edu
                Chen_Yan@URMC.rochester.edu
                m.doyley@rochester.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 September 2017
                21 September 2017
                2017
                : 7
                : 12081
                Affiliations
                [1 ]ISNI 0000 0004 1936 9166, GRID grid.412750.5, Aab Cardiovascular Research Institute, Department of Medicine, , University of Rochester School of Medicine and Dentistry, ; Rochester, NY USA
                [2 ]ISNI 0000 0004 1936 9166, GRID grid.412750.5, Department of Biomedical Genetics, , University of Rochester School of Medicine and Dentistry, ; Rochester, NY USA
                [3 ]ISNI 0000 0004 1936 9174, GRID grid.16416.34, Department of Electrical & Computer Engineering, , University of Rochester and Hajim School of Engineering & Applied Sciences, ; Rochester, NY USA
                Article
                12321
                10.1038/s41598-017-12321-7
                5608712
                28935983
                bf77138c-cabb-4528-b993-50a52eef0200
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 April 2017
                : 7 September 2017
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