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      Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe −/− mice

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          Abstract

          The calcium sensing receptor (CaSR) is a G-protein coupled receptor that especially plays an important role in the sensing of extracellular calcium to maintain its homeostasis. Several in-vitro studies demonstrated that CaSR plays a role in adipose tissue metabolism and inflammation, resulting in systemic inflammation and contributing to atherosclerosis development. The aim of this study was to investigate whether adipocyte CaSR plays a role in adipose tissue inflammation in-vivo and atherosclerosis development. By using a newly established conditional mature adipocyte specific CaSR deficient mouse on a hyperlipidemic and atherosclerosis prone Apoe −/− background it could be shown that CaSR deficiency in adipocytes does neither contribute to initiation nor to progression of atherosclerotic plaques as judged by the unchanged lesion size or composition. Additionally, CaSR deficiency did not influence gonadal visceral adipose tissue (vAT) inflammation in-vivo, although a small decrease in gonadal visceral adipose cholesterol content could be observed. In conclusion, adipocyte CaSR seems not to be involved in vAT inflammation in-vivo and does not influence atherosclerosis development in hyperlipidemic Apoe −/− mice.

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          Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance

          Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
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            Pathogenesis of atherosclerosis.

            Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease of medium-sized and large arteries fuelled by lipids. Endothelial cells, leukocytes, and intimal smooth muscle cells are the major players in the development of this disease. The most devastating consequences of atherosclerosis, such as heart attack and stroke, are caused by superimposed thrombosis. Therefore, the vital question is not why atherosclerosis develops but rather why atherosclerosis, after years of indolent growth, suddenly becomes complicated with luminal thrombosis. If thrombosis-prone plaques could be detected and thrombosis averted, atherosclerosis would be a much more benign disease. Approximately 76% of all fatal coronary thrombi are precipitated by plaque rupture. Plaque rupture is a more frequent cause of coronary thrombosis in men (approximately 80%) than in women (approximately 60%). Ruptured plaques are characterized by a large lipid-rich core, a thin fibrous cap that contains few smooth muscle cells and many macrophages, angiogenesis, adventitial inflammation, and outward remodeling. Plaque rupture is the most common cause of coronary thrombosis. Ruptured plaques and, by inference, rupture-prone plaques have characteristic pathoanatomical features that might be useful for their detection in vivo by imaging. This article describes the pathogenesis of atherosclerosis, how it begets thrombosis, and the possibility to detect thrombosis-prone plaques and prevent heart attack.
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              Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

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                Author and article information

                Contributors
                evandervorst@ukaachen.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 May 2021
                17 May 2021
                2021
                : 11
                : 10409
                Affiliations
                [1 ]GRID grid.1957.a, ISNI 0000 0001 0728 696X, Interdisciplinary Center for Clinical Research (IZKF), , RWTH Aachen University, ; Pauwelsstrasse 30, 52074 Aachen, Germany
                [2 ]GRID grid.1957.a, ISNI 0000 0001 0728 696X, Institute for Molecular Cardiovascular Research (IMCAR), , RWTH Aachen University, ; Aachen, Germany
                [3 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Pathology, , Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, ; Maastricht, The Netherlands
                [4 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute for Cardiovascular Prevention (IPEK), , Ludwig-Maximilians-University Munich, ; Munich, Germany
                [5 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, DZHK (German Centre for Cardiovascular Research), , Partner Site Munich Heart Alliance, ; Munich, Germany
                [6 ]GRID grid.412301.5, ISNI 0000 0000 8653 1507, Department of Internal Medicine I-Cardiology, , University Hospital Aachen, ; Aachen, Germany
                [7 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Biochemistry, , Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, ; Maastricht, The Netherlands
                [8 ]GRID grid.452617.3, Munich Cluster for Systems Neurology (SyNergy), ; Munich, Germany
                [9 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland
                Article
                89893
                10.1038/s41598-021-89893-y
                8128899
                34001955
                e93e78d4-71de-45c4-b58e-0616cc3fef38
                © The Author(s) 2021

                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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 September 2020
                : 4 May 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: SFB TRR219, C-03
                Award ID: SFB TRR219, M-03
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: AdG°692511
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100010447, Deutsches Zentrum für Herz-Kreislaufforschung;
                Award ID: 81Z0600202
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100005156, Alexander von Humboldt-Stiftung;
                Funded by: Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University
                Funded by: NWO-ZonMw Veni
                Award ID: 91619053
                Award Recipient :
                Funded by: RWTH Aachen University (3131)
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                cardiovascular biology,mechanisms of disease
                Uncategorized
                cardiovascular biology, mechanisms of disease

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