Perivascular Adipocytes Store Norepinephrine by Vesicular Transport
OBJECTIVE—Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is un...
Gespeichert in:
| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2019-02, Vol.39 (2), p.188-199 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 199 |
|---|---|
| container_issue | 2 |
| container_start_page | 188 |
| container_title | Arteriosclerosis, thrombosis, and vascular biology |
| container_volume | 39 |
| creator | Ahmad, Maleeha F Ferland, David Ayala-Lopez, Nadia Contreras, G Andres Darios, Emma Thompson, Janice Ismail, Alexander Thelen, Kyan Moeser, Adam J Burnett, Robert Anantharam, Arun Watts, Stephanie W |
| description | OBJECTIVE—Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).
APPROACH AND RESULTS—High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202—a functional and fluorescent VMAT probe—in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine.
CONCLUSIONS—This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension. |
| doi_str_mv | 10.1161/ATVBAHA.118.311720 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6344267</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>30567483</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4490-fa3eb157502f0ca5efe4523ceafbe0b7e4c773a671d5e8e548ccbabb9db982223</originalsourceid><addsrcrecordid>eNp9UE1Lw0AUXESxtfoHPEj-QOp-b3oRYlErFBWsvS67mxcbTZuwm7b03xtJLXrxMu8Nb2YeDEKXBA8JkeQ6nc1v00nakmTICFEUH6E-EZTHXDJ53O5YjWIhOe2hsxA-MMacUnyKegwLqXjC-mj8Ar7YmODWpfFRmhV15XYNhOi1qTxETy3UxQrqhW8xsrtoDqHoxDNvVqGufHOOTnJTBrjYzwF6u7-bjSfx9PnhcZxOY8f5CMe5YWCJUALTHDsjIAcuKHNgcgvYKuBOKWakIpmABARPnLPG2lFmRwmllA3QTZdbr-0SMgerxptS175YGr_TlSn038uqWOj3aqMl45xK1QbQLsD5KgQP-cFLsP6uVO8rbUmiu0pb09XvrwfLT4etQHaCbVU24MNnud6C1wswZbP4L_kLdC6G2g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Perivascular Adipocytes Store Norepinephrine by Vesicular Transport</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Ahmad, Maleeha F ; Ferland, David ; Ayala-Lopez, Nadia ; Contreras, G Andres ; Darios, Emma ; Thompson, Janice ; Ismail, Alexander ; Thelen, Kyan ; Moeser, Adam J ; Burnett, Robert ; Anantharam, Arun ; Watts, Stephanie W</creator><creatorcontrib>Ahmad, Maleeha F ; Ferland, David ; Ayala-Lopez, Nadia ; Contreras, G Andres ; Darios, Emma ; Thompson, Janice ; Ismail, Alexander ; Thelen, Kyan ; Moeser, Adam J ; Burnett, Robert ; Anantharam, Arun ; Watts, Stephanie W</creatorcontrib><description>OBJECTIVE—Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).
APPROACH AND RESULTS—High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202—a functional and fluorescent VMAT probe—in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine.
CONCLUSIONS—This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.118.311720</identifier><identifier>PMID: 30567483</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Adipocytes - metabolism ; Animals ; Biological Transport ; Chromaffin Cells - metabolism ; Female ; Male ; Mesenteric Arteries - metabolism ; Norepinephrine - metabolism ; Rats ; Rats, Sprague-Dawley ; Vesicular Monoamine Transport Proteins - physiology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2019-02, Vol.39 (2), p.188-199</ispartof><rights>2019 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4490-fa3eb157502f0ca5efe4523ceafbe0b7e4c773a671d5e8e548ccbabb9db982223</citedby><cites>FETCH-LOGICAL-c4490-fa3eb157502f0ca5efe4523ceafbe0b7e4c773a671d5e8e548ccbabb9db982223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30567483$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmad, Maleeha F</creatorcontrib><creatorcontrib>Ferland, David</creatorcontrib><creatorcontrib>Ayala-Lopez, Nadia</creatorcontrib><creatorcontrib>Contreras, G Andres</creatorcontrib><creatorcontrib>Darios, Emma</creatorcontrib><creatorcontrib>Thompson, Janice</creatorcontrib><creatorcontrib>Ismail, Alexander</creatorcontrib><creatorcontrib>Thelen, Kyan</creatorcontrib><creatorcontrib>Moeser, Adam J</creatorcontrib><creatorcontrib>Burnett, Robert</creatorcontrib><creatorcontrib>Anantharam, Arun</creatorcontrib><creatorcontrib>Watts, Stephanie W</creatorcontrib><title>Perivascular Adipocytes Store Norepinephrine by Vesicular Transport</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).
APPROACH AND RESULTS—High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202—a functional and fluorescent VMAT probe—in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine.
CONCLUSIONS—This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.</description><subject>Adipocytes - metabolism</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Chromaffin Cells - metabolism</subject><subject>Female</subject><subject>Male</subject><subject>Mesenteric Arteries - metabolism</subject><subject>Norepinephrine - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Vesicular Monoamine Transport Proteins - physiology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UE1Lw0AUXESxtfoHPEj-QOp-b3oRYlErFBWsvS67mxcbTZuwm7b03xtJLXrxMu8Nb2YeDEKXBA8JkeQ6nc1v00nakmTICFEUH6E-EZTHXDJ53O5YjWIhOe2hsxA-MMacUnyKegwLqXjC-mj8Ar7YmODWpfFRmhV15XYNhOi1qTxETy3UxQrqhW8xsrtoDqHoxDNvVqGufHOOTnJTBrjYzwF6u7-bjSfx9PnhcZxOY8f5CMe5YWCJUALTHDsjIAcuKHNgcgvYKuBOKWakIpmABARPnLPG2lFmRwmllA3QTZdbr-0SMgerxptS175YGr_TlSn038uqWOj3aqMl45xK1QbQLsD5KgQP-cFLsP6uVO8rbUmiu0pb09XvrwfLT4etQHaCbVU24MNnud6C1wswZbP4L_kLdC6G2g</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Ahmad, Maleeha F</creator><creator>Ferland, David</creator><creator>Ayala-Lopez, Nadia</creator><creator>Contreras, G Andres</creator><creator>Darios, Emma</creator><creator>Thompson, Janice</creator><creator>Ismail, Alexander</creator><creator>Thelen, Kyan</creator><creator>Moeser, Adam J</creator><creator>Burnett, Robert</creator><creator>Anantharam, Arun</creator><creator>Watts, Stephanie W</creator><general>American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>201902</creationdate><title>Perivascular Adipocytes Store Norepinephrine by Vesicular Transport</title><author>Ahmad, Maleeha F ; Ferland, David ; Ayala-Lopez, Nadia ; Contreras, G Andres ; Darios, Emma ; Thompson, Janice ; Ismail, Alexander ; Thelen, Kyan ; Moeser, Adam J ; Burnett, Robert ; Anantharam, Arun ; Watts, Stephanie W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4490-fa3eb157502f0ca5efe4523ceafbe0b7e4c773a671d5e8e548ccbabb9db982223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adipocytes - metabolism</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Chromaffin Cells - metabolism</topic><topic>Female</topic><topic>Male</topic><topic>Mesenteric Arteries - metabolism</topic><topic>Norepinephrine - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Vesicular Monoamine Transport Proteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmad, Maleeha F</creatorcontrib><creatorcontrib>Ferland, David</creatorcontrib><creatorcontrib>Ayala-Lopez, Nadia</creatorcontrib><creatorcontrib>Contreras, G Andres</creatorcontrib><creatorcontrib>Darios, Emma</creatorcontrib><creatorcontrib>Thompson, Janice</creatorcontrib><creatorcontrib>Ismail, Alexander</creatorcontrib><creatorcontrib>Thelen, Kyan</creatorcontrib><creatorcontrib>Moeser, Adam J</creatorcontrib><creatorcontrib>Burnett, Robert</creatorcontrib><creatorcontrib>Anantharam, Arun</creatorcontrib><creatorcontrib>Watts, Stephanie W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahmad, Maleeha F</au><au>Ferland, David</au><au>Ayala-Lopez, Nadia</au><au>Contreras, G Andres</au><au>Darios, Emma</au><au>Thompson, Janice</au><au>Ismail, Alexander</au><au>Thelen, Kyan</au><au>Moeser, Adam J</au><au>Burnett, Robert</au><au>Anantharam, Arun</au><au>Watts, Stephanie W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perivascular Adipocytes Store Norepinephrine by Vesicular Transport</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2019-02</date><risdate>2019</risdate><volume>39</volume><issue>2</issue><spage>188</spage><epage>199</epage><pages>188-199</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).
APPROACH AND RESULTS—High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202—a functional and fluorescent VMAT probe—in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine.
CONCLUSIONS—This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>30567483</pmid><doi>10.1161/ATVBAHA.118.311720</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2019-02, Vol.39 (2), p.188-199 |
| issn | 1079-5642 1524-4636 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6344267 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adipocytes - metabolism Animals Biological Transport Chromaffin Cells - metabolism Female Male Mesenteric Arteries - metabolism Norepinephrine - metabolism Rats Rats, Sprague-Dawley Vesicular Monoamine Transport Proteins - physiology |
| title | Perivascular Adipocytes Store Norepinephrine by Vesicular Transport |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T17%3A09%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Perivascular%20Adipocytes%20Store%20Norepinephrine%20by%20Vesicular%20Transport&rft.jtitle=Arteriosclerosis,%20thrombosis,%20and%20vascular%20biology&rft.au=Ahmad,%20Maleeha%20F&rft.date=2019-02&rft.volume=39&rft.issue=2&rft.spage=188&rft.epage=199&rft.pages=188-199&rft.issn=1079-5642&rft.eissn=1524-4636&rft_id=info:doi/10.1161/ATVBAHA.118.311720&rft_dat=%3Cpubmed_cross%3E30567483%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/30567483&rfr_iscdi=true |