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      Nerve-perivascular fat communication as a potential influence on the performance of blood vessels used as coronary artery bypass grafts

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          Abstract

          Perivascular fat, the cushion of adipose tissue surrounding blood vessels, possesses dilator, anti-contractile and constrictor actions. The majority of these effects have been demonstrated in vitro and may depend on the vessel and/or the experimental method or species used. In general, the relaxant effect of perivascular adipose tissue is local and may be either endothelium-dependent or endothelium-independent. However, nerve stimulation studies show that, in general, perivascular adipose tissue (PVAT) has an anti-contractile vascular effect likely to involve an action of the autonomic vascular nerves. Apart from a direct effect of perivascular fat-derived factors on bypass conduits, an interaction with a number of neurotransmitters and other agents may play an important role in graft performance. Although the vascular effects of PVAT are now well-established there is a lack of information regarding the role and/or involvement of peripheral nerves including autonomic nerves. For example, are perivascular adipocytes innervated and does PVAT affect neuronal control of vessels used as grafts? To date there is a paucity of electrophysiological studies into nerve-perivascular fat control. This review provides an overview of the vascular actions of PVAT, focussing on its potential relevance on blood vessels used as bypass grafts. In particular, the anatomical relationship between the perivascular nerves and fat are considered and the role of the perivascular-nerve/fat axis in the performance of bypass grafts is also discussed.

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          Most cited references78

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          Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases.

          Apolipoprotein (apo) E is a multifunctional protein with central roles in lipid metabolism, neurobiology, and neurodegenerative diseases. It has three major isoforms (apoE2, apoE3, and apoE4) with different effects on lipid and neuronal homeostasis. A major function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalize apoE-containing lipoprotein particles; thus, apoE participates in the distribution/redistribution of lipids among various tissues and cells of the body. In addition, intracellular apoE may modulate various cellular processes physiologically or pathophysiologically, including cytoskeletal assembly and stability, mitochondrial integrity and function, and dendritic morphology and function. Elucidation of the functional domains within this protein and of the three-dimensional structure of the major isoforms of apoE has contributed significantly to our understanding of its physiological and pathophysiological roles at a molecular level. It is likely that apoE, with its multiple cellular origins and multiple structural and biophysical properties, is involved widely in processes of lipid metabolism and neurobiology, possibly encompassing a variety of disorders of neuronal repair, remodeling, and degeneration by interacting with different factors through various pathways. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Periadventitial fat releases a vascular relaxing factor.

            Virtually all blood vessels are surrounded by adventitial fat. Adipocytes produce a host of vasoactive substances that may influence vascular contraction. We tested whether or not perivascular adipose tissue modulates contraction of aortic ring preparations. We studied aortic rings surrounded by periadventitial adipose tissue from adult Sprague-Dawley rats. At a maximum concentration of 300 nM angiotensin II, 6.5 microM serotonin, and 5 microM phenylephrine, the contractile response of intact rings was 95%, 80%, and 30% lower than that of vessels without periadventitial fat. The anticontractile effect of periadventitial fat was reduced by inhibition of ATP-dependent K+ channels with glibenclamide (3 microM) and by the tyrosine kinase inhibitor genistein (10 microM). Blocking NOS, cyclo-oxygenase, cytochrome P450, or adenosine receptors did not restore the vascular response in intact vessels. The anticontractile effect of perivascular fat was present in Zucker fa/fa rats, suggesting that leptin receptors were not responsible. Transferring the bath solution from intact vessels, isolated periadventitial tissue, and cultured rat adipocytes to precontracted vessels lacking periadventitial fat resulted in a rapid relaxation. We suggest that perivascular adventitial adipose tissue releases a transferable adventitium-derived relaxing factor that acts by tyrosine kinase-dependent activation of K+ channels in vascular smooth muscle cells.
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              Perivascular adipose tissue: more than just structural support.

              PVAT (perivascular adipose tissue) has recently been recognized as a novel factor in vascular biology, with implications in the pathophysiology of cardiovascular disease. Composed mainly of adipocytes, PVAT releases a wide range of biologically active molecules that modulate vascular smooth muscle cell contraction, proliferation and migration. PVAT exerts an anti-contractile effect in various vascular beds which seems to be mediated by an as yet elusive PVRF [PVAT-derived relaxing factor(s)]. Considerable progress has been made on deciphering the nature and mechanisms of action of PVRF, and the PVRFs proposed until now are reviewed here. However, complex pathways seem to regulate PVAT function and more than one mechanism is probably responsible for PVAT actions in vascular biology. The present review describes our current knowledge on the structure and function of PVAT, with a focus on its role in modulating vascular tone. Potential involvements of PVAT dysfunction in obesity, hypertension and atherosclerosis will be highlighted.
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                Author and article information

                Contributors
                ++44(0)20 7794 0500 , aloesch@talktalk.net , a.loesch@ucl.ac.uk
                m.dashwood@ucl.ac.uk
                Journal
                J Cell Commun Signal
                J Cell Commun Signal
                Journal of Cell Communication and Signaling
                Springer Netherlands (Dordrecht )
                1873-9601
                1873-961X
                10 June 2017
                10 June 2017
                March 2018
                : 12
                : 1
                : 181-191
                Affiliations
                [1 ]ISNI 0000000121901201, GRID grid.83440.3b, Centre for Rheumatology and Connective Tissue Diseases, Division of Medicine, , University College London Medical School, ; Royal Free Campus, Rowland Hill Street, NW3 2PF, London, UK
                [2 ]ISNI 0000000121901201, GRID grid.83440.3b, Division of Surgery and Interventional Science, Faculty of Medical Sciences, , University College London Medical School, ; Royal Free Campus, Rowland Hill Street, NW3 2PF, London, UK
                Author information
                http://orcid.org/0000-0002-8051-0099
                Article
                393
                10.1007/s12079-017-0393-7
                5842173
                28601937
                30491c9d-478e-431a-917f-228217e212c8
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.

                History
                : 1 May 2017
                : 9 May 2017
                Funding
                Funded by: University College London (UCL)
                Categories
                Research Article
                Custom metadata
                © The International CCN Society 2018

                Cell biology
                perivascular,nerves,adipose tissue,bypass grafts,vasoreactivity
                Cell biology
                perivascular, nerves, adipose tissue, bypass grafts, vasoreactivity

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