Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function
Objectives Chronic β1-adrenergic receptor (β1-AR)-calcium/calmodulin-dependent protein kinase II (CaMKII) activation leads to Ca2+ handling disturbances and adverse cardiac remodeling. We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial...
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| creator | Wenjuan, Xing Wenjun, Yan Peilin, Liu Haifeng, Zhang Feng, Gao |
| description | Objectives Chronic β1-adrenergic receptor (β1-AR)-calcium/calmodulin-dependent protein kinase II (CaMKII) activation leads to Ca2+ handling disturbances and adverse cardiac remodeling. We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial ischemia/reperfusion. This study attempted to determine whether insulin treatment influences the prolonged ischemic cardiac remodeling and function and the underlying mechanisms. Methods Myocardial infarction (MI) was induced by left coronary artery ligation in adult male rats. Sham and MI rats were randomly treated with saline, insulin (2 U/kg/d, hypo. daily), or insulin plus wortmannin (a PI3K inhibitor) for 4 wks. Results At the end of four weeks after the ischemia surgery, MI rats receiving insulin treatment showed increased cardiac ejection fraction (46.9 %±1.5 % vs 37.4%±2.4 %, p |
| doi_str_mv | 10.1136/heartjnl-2011-300867.213 |
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We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial ischemia/reperfusion. This study attempted to determine whether insulin treatment influences the prolonged ischemic cardiac remodeling and function and the underlying mechanisms. Methods Myocardial infarction (MI) was induced by left coronary artery ligation in adult male rats. Sham and MI rats were randomly treated with saline, insulin (2 U/kg/d, hypo. daily), or insulin plus wortmannin (a PI3K inhibitor) for 4 wks. Results At the end of four weeks after the ischemia surgery, MI rats receiving insulin treatment showed increased cardiac ejection fraction (46.9 %±1.5 % vs 37.4%±2.4 %, p<0.05), left ventricular developed pressure (LVDP) and positive maximal values of the first derivative of left ventricular pressure (+LV dP/dtmax) compared with those in saline group. Insulin-treated rats also showed a smaller LV cavity and thicker systolic interventricular septum. Although the general size and weight of heart were similar among four groups, the myocyte cross-sectional area was significantly increased in both saline and insulin groups. The pathologic hypertrophy-related proteins were decreased in insulin group (β-MHC, BNP, and ANP, all p<0.05). Moreover, insulin-treated rats showed increased PI3K p110 expression and Akt phosphorylation, and significantly decreased phosphorylation of phospholamban (Thr 17) and CaMKII both in basal and isoproterenol (ISO)-stimulated myocardial tissue (p<0.05). Importantly, inhibition of insulin signaling with wortmannin not only blocked insulin's inhibition of CaMKII, but also abolished the effects of insulin on cardiac structure and function (all p<0.05). Conclusion Chronic insulin treatment promotes physiological hypertrophy and restrains pathological hypertrophy and consequently improves prolonged function in post-ischemic hearts. This may, at least partially, be attributed to the inhibition of β1-AR-CaMKII activation by insulin-stimulated PI3K-Akt signaling.</description><identifier>ISSN: 1355-6037</identifier><identifier>EISSN: 1468-201X</identifier><identifier>DOI: 10.1136/heartjnl-2011-300867.213</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Cardiovascular Society</publisher><ispartof>Heart (British Cardiac Society), 2011-10, Vol.97 (Suppl 3), p.A73-A74</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Copyright: 2011 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://heart.bmj.com/content/97/Suppl_3/A73.3.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://heart.bmj.com/content/97/Suppl_3/A73.3.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3196,23571,27924,27925,77600,77631</link.rule.ids></links><search><creatorcontrib>Wenjuan, Xing</creatorcontrib><creatorcontrib>Wenjun, Yan</creatorcontrib><creatorcontrib>Peilin, Liu</creatorcontrib><creatorcontrib>Haifeng, Zhang</creatorcontrib><creatorcontrib>Feng, Gao</creatorcontrib><title>Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function</title><title>Heart (British Cardiac Society)</title><addtitle>Heart</addtitle><description>Objectives Chronic β1-adrenergic receptor (β1-AR)-calcium/calmodulin-dependent protein kinase II (CaMKII) activation leads to Ca2+ handling disturbances and adverse cardiac remodeling. We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial ischemia/reperfusion. This study attempted to determine whether insulin treatment influences the prolonged ischemic cardiac remodeling and function and the underlying mechanisms. Methods Myocardial infarction (MI) was induced by left coronary artery ligation in adult male rats. Sham and MI rats were randomly treated with saline, insulin (2 U/kg/d, hypo. daily), or insulin plus wortmannin (a PI3K inhibitor) for 4 wks. Results At the end of four weeks after the ischemia surgery, MI rats receiving insulin treatment showed increased cardiac ejection fraction (46.9 %±1.5 % vs 37.4%±2.4 %, p<0.05), left ventricular developed pressure (LVDP) and positive maximal values of the first derivative of left ventricular pressure (+LV dP/dtmax) compared with those in saline group. Insulin-treated rats also showed a smaller LV cavity and thicker systolic interventricular septum. Although the general size and weight of heart were similar among four groups, the myocyte cross-sectional area was significantly increased in both saline and insulin groups. The pathologic hypertrophy-related proteins were decreased in insulin group (β-MHC, BNP, and ANP, all p<0.05). Moreover, insulin-treated rats showed increased PI3K p110 expression and Akt phosphorylation, and significantly decreased phosphorylation of phospholamban (Thr 17) and CaMKII both in basal and isoproterenol (ISO)-stimulated myocardial tissue (p<0.05). Importantly, inhibition of insulin signaling with wortmannin not only blocked insulin's inhibition of CaMKII, but also abolished the effects of insulin on cardiac structure and function (all p<0.05). Conclusion Chronic insulin treatment promotes physiological hypertrophy and restrains pathological hypertrophy and consequently improves prolonged function in post-ischemic hearts. This may, at least partially, be attributed to the inhibition of β1-AR-CaMKII activation by insulin-stimulated PI3K-Akt signaling.</description><issn>1355-6037</issn><issn>1468-201X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkF2P1CAUhhujievqfyDxmhVKoe2lGb-6rmNM_LojB3qYYZzSEZiN-yv8y1KrXnt1CHne98BTVYSzK86FerZHiPkQjrRmnFPBWKfaq5qLe9UFb1S3XH-9X85CSqqYaB9Wj1I6MMaavlMX1c8h7L3x2c-BzI4YzMApjBEDxp23JKLFU54j3cC7t8NAwGZ_C79xc0eGkM5HH0iOCHnCkImfTnG-xUTKOM5hhyM5zSlTn-wep1JoIY4eluJpHrGEdwTCSNw52KX1cfXAwTHhkz_zsvr06uXHzRt68_71sHl-Q03NekEBVfkCrwEsOla3oxRKsq7tHRtB2VoKY7mUSrkGZVNb10HvhG2MAIO1MOKyerr2lnd-P2PK-jCfYygrNW871vK-iCtUt1I2zilFdPoU_QTxTnOmF_36r3696Nerfl30lyhdoz5l_PEvB_GbVq1opd5-3ujr7Zem__Biq68LL1beTIf_3_ILzL6dvQ</recordid><startdate>201110</startdate><enddate>201110</enddate><creator>Wenjuan, Xing</creator><creator>Wenjun, Yan</creator><creator>Peilin, Liu</creator><creator>Haifeng, Zhang</creator><creator>Feng, Gao</creator><general>BMJ Publishing Group Ltd and British Cardiovascular Society</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>201110</creationdate><title>Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function</title><author>Wenjuan, Xing ; Wenjun, Yan ; Peilin, Liu ; Haifeng, Zhang ; Feng, Gao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b2093-ae600012aacef027d53650879f0da6c253bc15566f4e542cf8a9f3c4b3abe23b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wenjuan, Xing</creatorcontrib><creatorcontrib>Wenjun, Yan</creatorcontrib><creatorcontrib>Peilin, Liu</creatorcontrib><creatorcontrib>Haifeng, Zhang</creatorcontrib><creatorcontrib>Feng, Gao</creatorcontrib><collection>Istex</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>Science Database (Alumni Edition)</collection><collection>STEM 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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>BMJ Journals</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science 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><jtitle>Heart (British Cardiac Society)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wenjuan, Xing</au><au>Wenjun, Yan</au><au>Peilin, Liu</au><au>Haifeng, Zhang</au><au>Feng, Gao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function</atitle><jtitle>Heart (British Cardiac Society)</jtitle><addtitle>Heart</addtitle><date>2011-10</date><risdate>2011</risdate><volume>97</volume><issue>Suppl 3</issue><spage>A73</spage><epage>A74</epage><pages>A73-A74</pages><issn>1355-6037</issn><eissn>1468-201X</eissn><abstract>Objectives Chronic β1-adrenergic receptor (β1-AR)-calcium/calmodulin-dependent protein kinase II (CaMKII) activation leads to Ca2+ handling disturbances and adverse cardiac remodeling. We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial ischemia/reperfusion. This study attempted to determine whether insulin treatment influences the prolonged ischemic cardiac remodeling and function and the underlying mechanisms. Methods Myocardial infarction (MI) was induced by left coronary artery ligation in adult male rats. Sham and MI rats were randomly treated with saline, insulin (2 U/kg/d, hypo. daily), or insulin plus wortmannin (a PI3K inhibitor) for 4 wks. Results At the end of four weeks after the ischemia surgery, MI rats receiving insulin treatment showed increased cardiac ejection fraction (46.9 %±1.5 % vs 37.4%±2.4 %, p<0.05), left ventricular developed pressure (LVDP) and positive maximal values of the first derivative of left ventricular pressure (+LV dP/dtmax) compared with those in saline group. Insulin-treated rats also showed a smaller LV cavity and thicker systolic interventricular septum. Although the general size and weight of heart were similar among four groups, the myocyte cross-sectional area was significantly increased in both saline and insulin groups. The pathologic hypertrophy-related proteins were decreased in insulin group (β-MHC, BNP, and ANP, all p<0.05). Moreover, insulin-treated rats showed increased PI3K p110 expression and Akt phosphorylation, and significantly decreased phosphorylation of phospholamban (Thr 17) and CaMKII both in basal and isoproterenol (ISO)-stimulated myocardial tissue (p<0.05). Importantly, inhibition of insulin signaling with wortmannin not only blocked insulin's inhibition of CaMKII, but also abolished the effects of insulin on cardiac structure and function (all p<0.05). Conclusion Chronic insulin treatment promotes physiological hypertrophy and restrains pathological hypertrophy and consequently improves prolonged function in post-ischemic hearts. This may, at least partially, be attributed to the inhibition of β1-AR-CaMKII activation by insulin-stimulated PI3K-Akt signaling.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Cardiovascular Society</pub><doi>10.1136/heartjnl-2011-300867.213</doi><oa>free_for_read</oa></addata></record> |
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| title | Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function |
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