Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients
Abstract Background Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox , but the underlying mechanism is still undefined. Aim To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin...
Gespeichert in:
| Veröffentlicht in: | Atherosclerosis 2010-11, Vol.213 (1), p.225-234 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 234 |
|---|---|
| container_issue | 1 |
| container_start_page | 225 |
| container_title | Atherosclerosis |
| container_volume | 213 |
| creator | Roberto, Carnevale Pasquale, Pignatelli Serena, Di Santo Simona, Bartimoccia Valerio, Sanguigni Laura, Napoleone Gaetano, Tanzilli Stefania, Basili Francesco, Violi |
| description | Abstract Background Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox , but the underlying mechanism is still undefined. Aim To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin. Methods and results We compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91phox serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91phox , urinary isoprostanes and platelet oxygen free radicals ( p < 0.001). In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47phox translocation to gp91phox and soluble gp91phox cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation. Conclusion This study provides the first evidence that in patients higher APN serum levels are associated with gp91phox down-regulation. APN-mediated gp91phox reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect. |
| doi_str_mv | 10.1016/j.atherosclerosis.2010.08.056 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_760233459</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021915010006994</els_id><sourcerecordid>760233459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c539t-2d94acf7a61d664ec11664172c427b5bdd425cec73792853de65bdd0082dc7853</originalsourceid><addsrcrecordid>eNqNkk1vEzEQhi1ERUPgL6C9VJw22F7v1wGkqIUWqaKVgLPl2BPisFkvHm8gF347s0raQ09cbGnmmQ-97zB2IfhCcFG92y5M2kAMaLvp9biQnHK8WfCyesZmoqnbXKhGPWczzqXIW1Hyc_YSccs5V7VoXrBzyZtC8krO2N9lCnFvMJnk-8z3G7_yCbPwxzuK7CHDFAEx23uTGeeH0IMlMt-B8yaBy74sr-5vjjxC5sLvPo_wY-yoOkwNs81hgGg3oQNMtHEHO2-zgdLQJ3zFztamQ3h9-ufs-6eP3y5v8tu768-Xy9vclkWbculaZey6NpVwVaXACkGfqKVVsl6VK-eULC3Yuqhb2ZSFg2oKct5IZ2sKzNnbY98hhl8jbaJ3Hi10nekhjKjrisuiUGVL5PsjaUldjLDWQ_Q7Ew9acD05oLf6iQN6ckDzRpMDVP_mNGlckUiP1Q-SE3BxAgxa062j6S31eOQKJdqG4Dm7PnJAuuw9RI2WNLMkfCQPtAv-v1f68KST7XzvafhPOABuwxh7El8LjVJz_XU6m-lqBB1M1baq-AfGmMaH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>760233459</pqid></control><display><type>article</type><title>Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Roberto, Carnevale ; Pasquale, Pignatelli ; Serena, Di Santo ; Simona, Bartimoccia ; Valerio, Sanguigni ; Laura, Napoleone ; Gaetano, Tanzilli ; Stefania, Basili ; Francesco, Violi</creator><creatorcontrib>Roberto, Carnevale ; Pasquale, Pignatelli ; Serena, Di Santo ; Simona, Bartimoccia ; Valerio, Sanguigni ; Laura, Napoleone ; Gaetano, Tanzilli ; Stefania, Basili ; Francesco, Violi</creatorcontrib><description>Abstract Background Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox , but the underlying mechanism is still undefined. Aim To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin. Methods and results We compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91phox serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91phox , urinary isoprostanes and platelet oxygen free radicals ( p < 0.001). In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47phox translocation to gp91phox and soluble gp91phox cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation. Conclusion This study provides the first evidence that in patients higher APN serum levels are associated with gp91phox down-regulation. APN-mediated gp91phox reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2010.08.056</identifier><identifier>PMID: 20832062</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Adiponectin ; Adiponectin - metabolism ; Aged ; Antioxidants - pharmacology ; Atherosclerosis (general aspects, experimental research) ; Atorvastatin Calcium ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Platelets - enzymology ; Cardiology. Vascular system ; Cardiovascular ; Cardiovascular system ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Free Radicals ; Heptanoic Acids - pharmacology ; Heptanoic Acids - therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Hypercholesterolemia - drug therapy ; Male ; Medical sciences ; Membrane Glycoproteins - metabolism ; Middle Aged ; NADPH oxidase ; NADPH Oxidase 2 ; NADPH Oxidases - metabolism ; Oxidative Stress ; Pharmacology. Drug treatments ; Platelets ; Pyrroles - pharmacology ; Pyrroles - therapeutic use ; Statins ; Vasodilator agents. Cerebral vasodilators</subject><ispartof>Atherosclerosis, 2010-11, Vol.213 (1), p.225-234</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2010 Elsevier Ireland Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-2d94acf7a61d664ec11664172c427b5bdd425cec73792853de65bdd0082dc7853</citedby><cites>FETCH-LOGICAL-c539t-2d94acf7a61d664ec11664172c427b5bdd425cec73792853de65bdd0082dc7853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915010006994$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23419808$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20832062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Roberto, Carnevale</creatorcontrib><creatorcontrib>Pasquale, Pignatelli</creatorcontrib><creatorcontrib>Serena, Di Santo</creatorcontrib><creatorcontrib>Simona, Bartimoccia</creatorcontrib><creatorcontrib>Valerio, Sanguigni</creatorcontrib><creatorcontrib>Laura, Napoleone</creatorcontrib><creatorcontrib>Gaetano, Tanzilli</creatorcontrib><creatorcontrib>Stefania, Basili</creatorcontrib><creatorcontrib>Francesco, Violi</creatorcontrib><title>Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Background Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox , but the underlying mechanism is still undefined. Aim To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin. Methods and results We compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91phox serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91phox , urinary isoprostanes and platelet oxygen free radicals ( p < 0.001). In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47phox translocation to gp91phox and soluble gp91phox cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation. Conclusion This study provides the first evidence that in patients higher APN serum levels are associated with gp91phox down-regulation. APN-mediated gp91phox reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect.</description><subject>Adiponectin</subject><subject>Adiponectin - metabolism</subject><subject>Aged</subject><subject>Antioxidants - pharmacology</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atorvastatin Calcium</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Platelets - enzymology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Cardiovascular system</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>Free Radicals</subject><subject>Heptanoic Acids - pharmacology</subject><subject>Heptanoic Acids - therapeutic use</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Hypercholesterolemia - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Middle Aged</subject><subject>NADPH oxidase</subject><subject>NADPH Oxidase 2</subject><subject>NADPH Oxidases - metabolism</subject><subject>Oxidative Stress</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelets</subject><subject>Pyrroles - pharmacology</subject><subject>Pyrroles - therapeutic use</subject><subject>Statins</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk1vEzEQhi1ERUPgL6C9VJw22F7v1wGkqIUWqaKVgLPl2BPisFkvHm8gF347s0raQ09cbGnmmQ-97zB2IfhCcFG92y5M2kAMaLvp9biQnHK8WfCyesZmoqnbXKhGPWczzqXIW1Hyc_YSccs5V7VoXrBzyZtC8krO2N9lCnFvMJnk-8z3G7_yCbPwxzuK7CHDFAEx23uTGeeH0IMlMt-B8yaBy74sr-5vjjxC5sLvPo_wY-yoOkwNs81hgGg3oQNMtHEHO2-zgdLQJ3zFztamQ3h9-ufs-6eP3y5v8tu768-Xy9vclkWbculaZey6NpVwVaXACkGfqKVVsl6VK-eULC3Yuqhb2ZSFg2oKct5IZ2sKzNnbY98hhl8jbaJ3Hi10nekhjKjrisuiUGVL5PsjaUldjLDWQ_Q7Ew9acD05oLf6iQN6ckDzRpMDVP_mNGlckUiP1Q-SE3BxAgxa062j6S31eOQKJdqG4Dm7PnJAuuw9RI2WNLMkfCQPtAv-v1f68KST7XzvafhPOABuwxh7El8LjVJz_XU6m-lqBB1M1baq-AfGmMaH</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Roberto, Carnevale</creator><creator>Pasquale, Pignatelli</creator><creator>Serena, Di Santo</creator><creator>Simona, Bartimoccia</creator><creator>Valerio, Sanguigni</creator><creator>Laura, Napoleone</creator><creator>Gaetano, Tanzilli</creator><creator>Stefania, Basili</creator><creator>Francesco, Violi</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20101101</creationdate><title>Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients</title><author>Roberto, Carnevale ; Pasquale, Pignatelli ; Serena, Di Santo ; Simona, Bartimoccia ; Valerio, Sanguigni ; Laura, Napoleone ; Gaetano, Tanzilli ; Stefania, Basili ; Francesco, Violi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-2d94acf7a61d664ec11664172c427b5bdd425cec73792853de65bdd0082dc7853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adiponectin</topic><topic>Adiponectin - metabolism</topic><topic>Aged</topic><topic>Antioxidants - pharmacology</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Atorvastatin Calcium</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Platelets - enzymology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular</topic><topic>Cardiovascular system</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>Free Radicals</topic><topic>Heptanoic Acids - pharmacology</topic><topic>Heptanoic Acids - therapeutic use</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Hypercholesterolemia - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Middle Aged</topic><topic>NADPH oxidase</topic><topic>NADPH Oxidase 2</topic><topic>NADPH Oxidases - metabolism</topic><topic>Oxidative Stress</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelets</topic><topic>Pyrroles - pharmacology</topic><topic>Pyrroles - therapeutic use</topic><topic>Statins</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roberto, Carnevale</creatorcontrib><creatorcontrib>Pasquale, Pignatelli</creatorcontrib><creatorcontrib>Serena, Di Santo</creatorcontrib><creatorcontrib>Simona, Bartimoccia</creatorcontrib><creatorcontrib>Valerio, Sanguigni</creatorcontrib><creatorcontrib>Laura, Napoleone</creatorcontrib><creatorcontrib>Gaetano, Tanzilli</creatorcontrib><creatorcontrib>Stefania, Basili</creatorcontrib><creatorcontrib>Francesco, Violi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roberto, Carnevale</au><au>Pasquale, Pignatelli</au><au>Serena, Di Santo</au><au>Simona, Bartimoccia</au><au>Valerio, Sanguigni</au><au>Laura, Napoleone</au><au>Gaetano, Tanzilli</au><au>Stefania, Basili</au><au>Francesco, Violi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>213</volume><issue>1</issue><spage>225</spage><epage>234</epage><pages>225-234</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Background Interventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox , but the underlying mechanism is still undefined. Aim To test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin. Methods and results We compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91phox serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91phox , urinary isoprostanes and platelet oxygen free radicals ( p < 0.001). In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47phox translocation to gp91phox and soluble gp91phox cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation. Conclusion This study provides the first evidence that in patients higher APN serum levels are associated with gp91phox down-regulation. APN-mediated gp91phox reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>20832062</pmid><doi>10.1016/j.atherosclerosis.2010.08.056</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9150 |
| ispartof | Atherosclerosis, 2010-11, Vol.213 (1), p.225-234 |
| issn | 0021-9150 1879-1484 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_760233459 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adiponectin Adiponectin - metabolism Aged Antioxidants - pharmacology Atherosclerosis (general aspects, experimental research) Atorvastatin Calcium Biological and medical sciences Blood and lymphatic vessels Blood Platelets - enzymology Cardiology. Vascular system Cardiovascular Cardiovascular system Case-Control Studies Cross-Sectional Studies Female Free Radicals Heptanoic Acids - pharmacology Heptanoic Acids - therapeutic use Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Hypercholesterolemia - drug therapy Male Medical sciences Membrane Glycoproteins - metabolism Middle Aged NADPH oxidase NADPH Oxidase 2 NADPH Oxidases - metabolism Oxidative Stress Pharmacology. Drug treatments Platelets Pyrroles - pharmacology Pyrroles - therapeutic use Statins Vasodilator agents. Cerebral vasodilators |
| title | Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T20%3A51%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Atorvastatin%20inhibits%20oxidative%20stress%20via%20adiponectin-mediated%20NADPH%20oxidase%20down-regulation%20in%20hypercholesterolemic%20patients&rft.jtitle=Atherosclerosis&rft.au=Roberto,%20Carnevale&rft.date=2010-11-01&rft.volume=213&rft.issue=1&rft.spage=225&rft.epage=234&rft.pages=225-234&rft.issn=0021-9150&rft.eissn=1879-1484&rft_id=info:doi/10.1016/j.atherosclerosis.2010.08.056&rft_dat=%3Cproquest_cross%3E760233459%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=760233459&rft_id=info:pmid/20832062&rft_els_id=S0021915010006994&rfr_iscdi=true |