Deletion of AMPK[alpha]1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release
Background and Purpose Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular eff...
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Veröffentlicht in: | British journal of pharmacology 2017-10, Vol.174 (20), p.3398 |
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description | Background and Purpose Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Experimental Approach Endothelium-denuded aortic rings from wild-type (WT; Sv129) and [alpha]1AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPK[alpha]1 KO on the secretory profile of PVAT was assessed by elisa. Key Results Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. Conclusions and Implications AMPK[alpha]1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc |
doi_str_mv | 10.1111/bph.13633 |
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AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Experimental Approach Endothelium-denuded aortic rings from wild-type (WT; Sv129) and [alpha]1AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPK[alpha]1 KO on the secretory profile of PVAT was assessed by elisa. Key Results Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. Conclusions and Implications AMPK[alpha]1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.13633</identifier><language>eng</language><publisher>London: Blackwell Publishing Ltd</publisher><subject>Adiponectin ; Adipose tissue ; Adipose tissue (brown) ; Aorta ; Blood vessels ; Clonal deletion ; Endothelium ; Energy balance ; Enzyme-linked immunosorbent assay ; Molecular modelling ; Rodents ; Secretion ; Thorax</subject><ispartof>British journal of pharmacology, 2017-10, Vol.174 (20), p.3398</ispartof><rights>2017 The British Pharmacological Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Almabrouk, Tarek A M</creatorcontrib><creatorcontrib>Ugusman, Azizah B</creatorcontrib><creatorcontrib>Katwan, Omar J</creatorcontrib><creatorcontrib>Salt, Ian P</creatorcontrib><creatorcontrib>Kennedy, Simon</creatorcontrib><title>Deletion of AMPK[alpha]1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release</title><title>British journal of pharmacology</title><description>Background and Purpose Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Experimental Approach Endothelium-denuded aortic rings from wild-type (WT; Sv129) and [alpha]1AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPK[alpha]1 KO on the secretory profile of PVAT was assessed by elisa. Key Results Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. Conclusions and Implications AMPK[alpha]1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc</description><subject>Adiponectin</subject><subject>Adipose tissue</subject><subject>Adipose tissue (brown)</subject><subject>Aorta</subject><subject>Blood vessels</subject><subject>Clonal deletion</subject><subject>Endothelium</subject><subject>Energy balance</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Molecular modelling</subject><subject>Rodents</subject><subject>Secretion</subject><subject>Thorax</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqNjMFKAzEYhIMouFYPvkHAix62Js12dz0WrQhS6KF4ESm_2X_ZlJDE5I9P4IMbxQdwLgMz8w1jl1LMZdHte5jmUrVKHbFKNl1bL1Uvj1klhOhqKfv-lJ2ldBCilN2yYl8PaJGMd9yPfLXZPr-CDRO8SQ5E6DIQJk4TcnBktHcUQZOxyHEcUdMPFTCaT0g6W4gcBhN8Qk4mpYz8evuy2t0UeOARh6zL2e_CFda4klmEhOfsZASb8OLPZ-zqcb27f6pD9B8ZE-0PPkdXqr28axZtsxBtp_63-gbk8ldM</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Almabrouk, Tarek A M</creator><creator>Ugusman, Azizah B</creator><creator>Katwan, Omar J</creator><creator>Salt, Ian P</creator><creator>Kennedy, Simon</creator><general>Blackwell Publishing Ltd</general><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20171001</creationdate><title>Deletion of AMPK[alpha]1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release</title><author>Almabrouk, Tarek A M ; Ugusman, Azizah B ; Katwan, Omar J ; Salt, Ian P ; Kennedy, Simon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_19426420673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adiponectin</topic><topic>Adipose tissue</topic><topic>Adipose tissue (brown)</topic><topic>Aorta</topic><topic>Blood vessels</topic><topic>Clonal deletion</topic><topic>Endothelium</topic><topic>Energy balance</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Molecular modelling</topic><topic>Rodents</topic><topic>Secretion</topic><topic>Thorax</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Almabrouk, Tarek A M</creatorcontrib><creatorcontrib>Ugusman, Azizah B</creatorcontrib><creatorcontrib>Katwan, Omar J</creatorcontrib><creatorcontrib>Salt, Ian P</creatorcontrib><creatorcontrib>Kennedy, Simon</creatorcontrib><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Almabrouk, Tarek A M</au><au>Ugusman, Azizah B</au><au>Katwan, Omar J</au><au>Salt, Ian P</au><au>Kennedy, Simon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deletion of AMPK[alpha]1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release</atitle><jtitle>British journal of pharmacology</jtitle><date>2017-10-01</date><risdate>2017</risdate><volume>174</volume><issue>20</issue><spage>3398</spage><pages>3398-</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and Purpose Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Experimental Approach Endothelium-denuded aortic rings from wild-type (WT; Sv129) and [alpha]1AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPK[alpha]1 KO on the secretory profile of PVAT was assessed by elisa. Key Results Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. Conclusions and Implications AMPK[alpha]1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc</abstract><cop>London</cop><pub>Blackwell Publishing Ltd</pub><doi>10.1111/bph.13633</doi></addata></record> |
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subjects | Adiponectin Adipose tissue Adipose tissue (brown) Aorta Blood vessels Clonal deletion Endothelium Energy balance Enzyme-linked immunosorbent assay Molecular modelling Rodents Secretion Thorax |
title | Deletion of AMPK[alpha]1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release |
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