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Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction
Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltratio...
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Published in: | Basic research in cardiology 2019-03, Vol.114 (2), p.8-12, Article 8 |
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creator | Kröller-Schön, Swenja Jansen, Thomas Tran, Thi Lan P. Kvandová, Miroslawa Kalinovic, Sanela Oelze, Matthias Keaney, John F. Foretz, Marc Viollet, Benoit Daiber, Andreas Kossmann, Sabine Lagrange, Jeremy Frenis, Katie Wenzel, Philip Münzel, Thomas Schulz, Eberhard |
description | Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPK
flox/flox
mice with TekCre
+
or Cadh5Cre
+
mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2
+
T-cells, CD11b
+
F4/80
+
macrophages and Ly6G
−
Ly6C
+
monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment. |
doi_str_mv | 10.1007/s00395-019-0717-2 |
format | article |
fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_02348817v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2166927467</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3872-2a90a07b160d8cf191fb4c318651d23e96ccb3cb55ee8fcfef58de73208476cc3</originalsourceid><addsrcrecordid>eNp1kc9u1DAQhy0EokvhAbigSFzKwTBjJ7ZzXFWFrroIDnDiYDmO3bpK7BInlfpYvAjPhFcprYTEyfLMNz__-Qh5jfAeAeSHDMDbhgK2FCRKyp6QDda8oaiAPyUb4ABU1UwdkRc5XwNgLQQ-J0ccRM1boTbkx1ns03zlhmCG6vcv3H7-elGNqV8GM7tcmXgZ0uxiDrHa7ejo-lDqfXVrsi3IVIXoBzOOZg4pFrqv-rvsl2gP-5fkmTdDdq_u12Py_ePZt9Nzuv_yaXe63VPLlWSUmRYMyA4F9Mp6bNF3teWoRIM9464V1nbcdk3jnPLWO9-o3knOQNWy9PgxebfmXplB30xhNNOdTibo8-1eH2rAeK0Uylss7MnK3kzp5-LyrMeQrRsGE11asmYoWy4Yq1VB3_6DXqdliuUlhRKiZbIWslC4UnZKOU_OP9wAQR8s6dWSLpb0wZJmZebNffLSlS99mPirpQBsBXJpxUs3PR79_9Q_StGckg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2166927467</pqid></control><display><type>article</type><title>Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction</title><source>Springer Link</source><creator>Kröller-Schön, Swenja ; Jansen, Thomas ; Tran, Thi Lan P. ; Kvandová, Miroslawa ; Kalinovic, Sanela ; Oelze, Matthias ; Keaney, John F. ; Foretz, Marc ; Viollet, Benoit ; Daiber, Andreas ; Kossmann, Sabine ; Lagrange, Jeremy ; Frenis, Katie ; Wenzel, Philip ; Münzel, Thomas ; Schulz, Eberhard</creator><creatorcontrib>Kröller-Schön, Swenja ; Jansen, Thomas ; Tran, Thi Lan P. ; Kvandová, Miroslawa ; Kalinovic, Sanela ; Oelze, Matthias ; Keaney, John F. ; Foretz, Marc ; Viollet, Benoit ; Daiber, Andreas ; Kossmann, Sabine ; Lagrange, Jeremy ; Frenis, Katie ; Wenzel, Philip ; Münzel, Thomas ; Schulz, Eberhard</creatorcontrib><description>Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPK
flox/flox
mice with TekCre
+
or Cadh5Cre
+
mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2
+
T-cells, CD11b
+
F4/80
+
macrophages and Ly6G
−
Ly6C
+
monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment.</description><identifier>ISSN: 0300-8428</identifier><identifier>EISSN: 1435-1803</identifier><identifier>DOI: 10.1007/s00395-019-0717-2</identifier><identifier>PMID: 30643968</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>AMP-Activated Protein Kinases ; Angiotensin ; Angiotensin II ; Animals ; Antioxidants ; Aorta ; Biochemistry ; Biochemistry, Molecular Biology ; Breeding ; Cardiology ; CD11b antigen ; CD90 antigen ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Clonal deletion ; Endocrinology and metabolism ; Endothelium, Vascular ; Flow cytometry ; Flox ; Gene expression ; Heme ; Heme Oxygenase-1 ; Human health and pathology ; Infiltration ; Inflammation ; Leukocytes ; Life Sciences ; Lymphocytes T ; Macrophages ; Male ; Medicine ; Medicine & Public Health ; Membrane Proteins ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular biology ; Monocyte chemoattractant protein ; Monocyte chemoattractant protein 1 ; Monocytes ; NAD(P)H oxidase ; Original Contribution ; Oxidative Stress ; Oxygenase ; Phagocytes ; Proteins ; Rodents ; Vascular cell adhesion molecule 1</subject><ispartof>Basic research in cardiology, 2019-03, Vol.114 (2), p.8-12, Article 8</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>Basic Research in Cardiology is a copyright of Springer, (2019). All Rights Reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3872-2a90a07b160d8cf191fb4c318651d23e96ccb3cb55ee8fcfef58de73208476cc3</citedby><cites>FETCH-LOGICAL-c3872-2a90a07b160d8cf191fb4c318651d23e96ccb3cb55ee8fcfef58de73208476cc3</cites><orcidid>0000-0002-5397-2781 ; 0000-0001-7017-9032 ; 0000-0002-1403-0978 ; 0000-0002-0811-565X ; 0000-0002-0121-0224 ; 0000-0002-2769-0094 ; 0000-0001-6066-6080</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30643968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02348817$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Kröller-Schön, Swenja</creatorcontrib><creatorcontrib>Jansen, Thomas</creatorcontrib><creatorcontrib>Tran, Thi Lan P.</creatorcontrib><creatorcontrib>Kvandová, Miroslawa</creatorcontrib><creatorcontrib>Kalinovic, Sanela</creatorcontrib><creatorcontrib>Oelze, Matthias</creatorcontrib><creatorcontrib>Keaney, John F.</creatorcontrib><creatorcontrib>Foretz, Marc</creatorcontrib><creatorcontrib>Viollet, Benoit</creatorcontrib><creatorcontrib>Daiber, Andreas</creatorcontrib><creatorcontrib>Kossmann, Sabine</creatorcontrib><creatorcontrib>Lagrange, Jeremy</creatorcontrib><creatorcontrib>Frenis, Katie</creatorcontrib><creatorcontrib>Wenzel, Philip</creatorcontrib><creatorcontrib>Münzel, Thomas</creatorcontrib><creatorcontrib>Schulz, Eberhard</creatorcontrib><title>Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction</title><title>Basic research in cardiology</title><addtitle>Basic Res Cardiol</addtitle><addtitle>Basic Res Cardiol</addtitle><description>Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPK
flox/flox
mice with TekCre
+
or Cadh5Cre
+
mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2
+
T-cells, CD11b
+
F4/80
+
macrophages and Ly6G
−
Ly6C
+
monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment.</description><subject>AMP-Activated Protein Kinases</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Aorta</subject><subject>Biochemistry</subject><subject>Biochemistry, Molecular Biology</subject><subject>Breeding</subject><subject>Cardiology</subject><subject>CD11b antigen</subject><subject>CD90 antigen</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell adhesion molecules</subject><subject>Clonal deletion</subject><subject>Endocrinology and metabolism</subject><subject>Endothelium, Vascular</subject><subject>Flow cytometry</subject><subject>Flox</subject><subject>Gene expression</subject><subject>Heme</subject><subject>Heme Oxygenase-1</subject><subject>Human health and pathology</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Leukocytes</subject><subject>Life Sciences</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular biology</subject><subject>Monocyte chemoattractant protein</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>NAD(P)H oxidase</subject><subject>Original Contribution</subject><subject>Oxidative Stress</subject><subject>Oxygenase</subject><subject>Phagocytes</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Vascular cell adhesion molecule 1</subject><issn>0300-8428</issn><issn>1435-1803</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kc9u1DAQhy0EokvhAbigSFzKwTBjJ7ZzXFWFrroIDnDiYDmO3bpK7BInlfpYvAjPhFcprYTEyfLMNz__-Qh5jfAeAeSHDMDbhgK2FCRKyp6QDda8oaiAPyUb4ABU1UwdkRc5XwNgLQQ-J0ccRM1boTbkx1ns03zlhmCG6vcv3H7-elGNqV8GM7tcmXgZ0uxiDrHa7ejo-lDqfXVrsi3IVIXoBzOOZg4pFrqv-rvsl2gP-5fkmTdDdq_u12Py_ePZt9Nzuv_yaXe63VPLlWSUmRYMyA4F9Mp6bNF3teWoRIM9464V1nbcdk3jnPLWO9-o3knOQNWy9PgxebfmXplB30xhNNOdTibo8-1eH2rAeK0Uylss7MnK3kzp5-LyrMeQrRsGE11asmYoWy4Yq1VB3_6DXqdliuUlhRKiZbIWslC4UnZKOU_OP9wAQR8s6dWSLpb0wZJmZebNffLSlS99mPirpQBsBXJpxUs3PR79_9Q_StGckg</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Kröller-Schön, Swenja</creator><creator>Jansen, Thomas</creator><creator>Tran, Thi Lan P.</creator><creator>Kvandová, Miroslawa</creator><creator>Kalinovic, Sanela</creator><creator>Oelze, Matthias</creator><creator>Keaney, John F.</creator><creator>Foretz, Marc</creator><creator>Viollet, Benoit</creator><creator>Daiber, Andreas</creator><creator>Kossmann, Sabine</creator><creator>Lagrange, Jeremy</creator><creator>Frenis, Katie</creator><creator>Wenzel, Philip</creator><creator>Münzel, Thomas</creator><creator>Schulz, Eberhard</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5397-2781</orcidid><orcidid>https://orcid.org/0000-0001-7017-9032</orcidid><orcidid>https://orcid.org/0000-0002-1403-0978</orcidid><orcidid>https://orcid.org/0000-0002-0811-565X</orcidid><orcidid>https://orcid.org/0000-0002-0121-0224</orcidid><orcidid>https://orcid.org/0000-0002-2769-0094</orcidid><orcidid>https://orcid.org/0000-0001-6066-6080</orcidid></search><sort><creationdate>20190301</creationdate><title>Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction</title><author>Kröller-Schön, Swenja ; Jansen, Thomas ; Tran, Thi Lan P. ; Kvandová, Miroslawa ; Kalinovic, Sanela ; Oelze, Matthias ; Keaney, John F. ; Foretz, Marc ; Viollet, Benoit ; Daiber, Andreas ; Kossmann, Sabine ; Lagrange, Jeremy ; Frenis, Katie ; Wenzel, Philip ; Münzel, Thomas ; Schulz, Eberhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3872-2a90a07b160d8cf191fb4c318651d23e96ccb3cb55ee8fcfef58de73208476cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>AMP-Activated Protein Kinases</topic><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Aorta</topic><topic>Biochemistry</topic><topic>Biochemistry, Molecular Biology</topic><topic>Breeding</topic><topic>Cardiology</topic><topic>CD11b antigen</topic><topic>CD90 antigen</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell adhesion molecules</topic><topic>Clonal deletion</topic><topic>Endocrinology and metabolism</topic><topic>Endothelium, Vascular</topic><topic>Flow cytometry</topic><topic>Flox</topic><topic>Gene expression</topic><topic>Heme</topic><topic>Heme Oxygenase-1</topic><topic>Human health and pathology</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Leukocytes</topic><topic>Life Sciences</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular biology</topic><topic>Monocyte chemoattractant protein</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>NAD(P)H oxidase</topic><topic>Original Contribution</topic><topic>Oxidative Stress</topic><topic>Oxygenase</topic><topic>Phagocytes</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Vascular cell adhesion molecule 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kröller-Schön, Swenja</creatorcontrib><creatorcontrib>Jansen, Thomas</creatorcontrib><creatorcontrib>Tran, Thi Lan P.</creatorcontrib><creatorcontrib>Kvandová, Miroslawa</creatorcontrib><creatorcontrib>Kalinovic, Sanela</creatorcontrib><creatorcontrib>Oelze, Matthias</creatorcontrib><creatorcontrib>Keaney, John F.</creatorcontrib><creatorcontrib>Foretz, Marc</creatorcontrib><creatorcontrib>Viollet, Benoit</creatorcontrib><creatorcontrib>Daiber, Andreas</creatorcontrib><creatorcontrib>Kossmann, Sabine</creatorcontrib><creatorcontrib>Lagrange, Jeremy</creatorcontrib><creatorcontrib>Frenis, Katie</creatorcontrib><creatorcontrib>Wenzel, Philip</creatorcontrib><creatorcontrib>Münzel, Thomas</creatorcontrib><creatorcontrib>Schulz, Eberhard</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection (ProQuest Medical & Health Databases)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Basic research in cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kröller-Schön, Swenja</au><au>Jansen, Thomas</au><au>Tran, Thi Lan P.</au><au>Kvandová, Miroslawa</au><au>Kalinovic, Sanela</au><au>Oelze, Matthias</au><au>Keaney, John F.</au><au>Foretz, Marc</au><au>Viollet, Benoit</au><au>Daiber, Andreas</au><au>Kossmann, Sabine</au><au>Lagrange, Jeremy</au><au>Frenis, Katie</au><au>Wenzel, Philip</au><au>Münzel, Thomas</au><au>Schulz, Eberhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction</atitle><jtitle>Basic research in cardiology</jtitle><stitle>Basic Res Cardiol</stitle><addtitle>Basic Res Cardiol</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>114</volume><issue>2</issue><spage>8</spage><epage>12</epage><pages>8-12</pages><artnum>8</artnum><issn>0300-8428</issn><eissn>1435-1803</eissn><abstract>Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPK
flox/flox
mice with TekCre
+
or Cadh5Cre
+
mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2
+
T-cells, CD11b
+
F4/80
+
macrophages and Ly6G
−
Ly6C
+
monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30643968</pmid><doi>10.1007/s00395-019-0717-2</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5397-2781</orcidid><orcidid>https://orcid.org/0000-0001-7017-9032</orcidid><orcidid>https://orcid.org/0000-0002-1403-0978</orcidid><orcidid>https://orcid.org/0000-0002-0811-565X</orcidid><orcidid>https://orcid.org/0000-0002-0121-0224</orcidid><orcidid>https://orcid.org/0000-0002-2769-0094</orcidid><orcidid>https://orcid.org/0000-0001-6066-6080</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0300-8428 |
ispartof | Basic research in cardiology, 2019-03, Vol.114 (2), p.8-12, Article 8 |
issn | 0300-8428 1435-1803 |
language | eng |
recordid | cdi_hal_primary_oai_HAL_hal_02348817v1 |
source | Springer Link |
subjects | AMP-Activated Protein Kinases Angiotensin Angiotensin II Animals Antioxidants Aorta Biochemistry Biochemistry, Molecular Biology Breeding Cardiology CD11b antigen CD90 antigen Cell adhesion Cell adhesion & migration Cell adhesion molecules Clonal deletion Endocrinology and metabolism Endothelium, Vascular Flow cytometry Flox Gene expression Heme Heme Oxygenase-1 Human health and pathology Infiltration Inflammation Leukocytes Life Sciences Lymphocytes T Macrophages Male Medicine Medicine & Public Health Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Molecular biology Monocyte chemoattractant protein Monocyte chemoattractant protein 1 Monocytes NAD(P)H oxidase Original Contribution Oxidative Stress Oxygenase Phagocytes Proteins Rodents Vascular cell adhesion molecule 1 |
title | Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction |
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