Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure
Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility an...
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| Veröffentlicht in: | International journal of molecular sciences 2014-08, Vol.15 (8), p.14803-14818 |
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| creator | Cho, Kyoung-Im Koo, Sang-Ho Cha, Tae-Joon Heo, Jung-Ho Kim, Hyun-Su Jo, Gee-Bum Lee, Jae-Woo |
| description | Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes. |
| doi_str_mv | 10.3390/ijms150814803 |
| format | Article |
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We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms150814803</identifier><identifier>PMID: 25153633</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Atrial Fibrillation - drug therapy ; Atrial Fibrillation - metabolism ; Blotting, Western ; Cardiac arrhythmia ; Echocardiography ; Heart failure ; Heart Failure - drug therapy ; Heart Failure - metabolism ; Immunohistochemistry ; Male ; Nitric Oxide Synthase Type II - metabolism ; Nitric Oxide Synthase Type III - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Pharmacology ; Rats ; Rats, Sprague-Dawley ; Rodents ; Simvastatin - therapeutic use ; Statins</subject><ispartof>International journal of molecular sciences, 2014-08, Vol.15 (8), p.14803-14818</ispartof><rights>Copyright MDPI AG 2014</rights><rights>2014 by the authors; licensee MDPI, Basel, Switzerland. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-1ddd9de73b8c8d363461d89454c1d536b091d6f93f56fc2ec2aa0081d34cadc23</citedby><cites>FETCH-LOGICAL-c415t-1ddd9de73b8c8d363461d89454c1d536b091d6f93f56fc2ec2aa0081d34cadc23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159883/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159883/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25153633$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Kyoung-Im</creatorcontrib><creatorcontrib>Koo, Sang-Ho</creatorcontrib><creatorcontrib>Cha, Tae-Joon</creatorcontrib><creatorcontrib>Heo, Jung-Ho</creatorcontrib><creatorcontrib>Kim, Hyun-Su</creatorcontrib><creatorcontrib>Jo, Gee-Bum</creatorcontrib><creatorcontrib>Lee, Jae-Woo</creatorcontrib><title>Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.</description><subject>Animals</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrial Fibrillation - metabolism</subject><subject>Blotting, Western</subject><subject>Cardiac arrhythmia</subject><subject>Echocardiography</subject><subject>Heart failure</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - metabolism</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Simvastatin - therapeutic use</subject><subject>Statins</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1vFSEUhonR2A9dujUkblw4lo9hLrMxMY1WkyZdVNcTBs70nhsGKjA39sf4X2Xa2rSuIJyH5_ByCHnD2Ucpe3aCuzlzxTRvNZPPyCFvhWgY6zbPH-0PyFHOO8aEFKp_SQ6E4kp2Uh6SP5c4700upmCgphQIiymQadkCjb_R1fM90FwS5PyBQnCxVjwaX4kU5zFeQUCL5Yaa4G5vYXCLxRH9ehinKk0rPuGY0Pvqi4GuvWgyhc7RgV8pzHYLM1q6BZMKnQz6JcEr8mIyPsPr-_WY_Pz65cfpt-b84uz76efzxrZclYY753oHGzlqq10N1nbc6b5VreWuBh1Zz1039XJS3WQFWGEMq1_mZGuNs0Iek0933utlnMFZCCUZP1wnnE26GaLB4Wkl4Ha4ivuhtu-1llXw_l6Q4q8Fchnmmghq3gBxyQNXasO00FJX9N1_6C4uKdR4lep4lYl2FTZ3lE0x5wTTw2M4G9bBD08GX_m3jxM80P8mLf8Ccjaukw</recordid><startdate>20140822</startdate><enddate>20140822</enddate><creator>Cho, Kyoung-Im</creator><creator>Koo, Sang-Ho</creator><creator>Cha, Tae-Joon</creator><creator>Heo, Jung-Ho</creator><creator>Kim, Hyun-Su</creator><creator>Jo, Gee-Bum</creator><creator>Lee, Jae-Woo</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140822</creationdate><title>Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure</title><author>Cho, Kyoung-Im ; Koo, Sang-Ho ; Cha, Tae-Joon ; Heo, Jung-Ho ; Kim, Hyun-Su ; Jo, Gee-Bum ; Lee, Jae-Woo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-1ddd9de73b8c8d363461d89454c1d536b091d6f93f56fc2ec2aa0081d34cadc23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrial Fibrillation - metabolism</topic><topic>Blotting, Western</topic><topic>Cardiac arrhythmia</topic><topic>Echocardiography</topic><topic>Heart failure</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - metabolism</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Simvastatin - therapeutic use</topic><topic>Statins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Kyoung-Im</creatorcontrib><creatorcontrib>Koo, Sang-Ho</creatorcontrib><creatorcontrib>Cha, Tae-Joon</creatorcontrib><creatorcontrib>Heo, Jung-Ho</creatorcontrib><creatorcontrib>Kim, Hyun-Su</creatorcontrib><creatorcontrib>Jo, Gee-Bum</creatorcontrib><creatorcontrib>Lee, Jae-Woo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Kyoung-Im</au><au>Koo, Sang-Ho</au><au>Cha, Tae-Joon</au><au>Heo, Jung-Ho</au><au>Kim, Hyun-Su</au><au>Jo, Gee-Bum</au><au>Lee, Jae-Woo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2014-08-22</date><risdate>2014</risdate><volume>15</volume><issue>8</issue><spage>14803</spage><epage>14818</epage><pages>14803-14818</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>25153633</pmid><doi>10.3390/ijms150814803</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Atrial Fibrillation - drug therapy Atrial Fibrillation - metabolism Blotting, Western Cardiac arrhythmia Echocardiography Heart failure Heart Failure - drug therapy Heart Failure - metabolism Immunohistochemistry Male Nitric Oxide Synthase Type II - metabolism Nitric Oxide Synthase Type III - metabolism Oxidative stress Oxidative Stress - drug effects Pharmacology Rats Rats, Sprague-Dawley Rodents Simvastatin - therapeutic use Statins |
| title | Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure |
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