Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis

Background: Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. Aim: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac...

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Veröffentlicht in:European journal of heart failure 2007-04, Vol.9 (4), p.343-351
Hauptverfasser: Ruixing, Yin, Dezhai, Yang, Hai, Wu, Kai, Huang, Xianghong, Wu, Yuming, Chen
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container_end_page 351
container_issue 4
container_start_page 343
container_title European journal of heart failure
container_volume 9
creator Ruixing, Yin
Dezhai, Yang
Hai, Wu
Kai, Huang
Xianghong, Wu
Yuming, Chen
description Background: Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. Aim: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Methods: Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection. Results: Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P
doi_str_mv 10.1016/j.ejheart.2006.10.007
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However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. Aim: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Methods: Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection. Results: Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P&lt;0.05 to 0.01). Apoptotic index in the treated group was less than in the control (P&lt;0.01). Caspase-3 activation and mitochondrial cytochrome c release in the treated group were also lower than in the control (P&lt;0.01). VEGF165 cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium. Conclusion: Intramyocardial injection of VEGF165 cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction.</description><identifier>ISSN: 1388-9842</identifier><identifier>EISSN: 1879-0844</identifier><identifier>DOI: 10.1016/j.ejheart.2006.10.007</identifier><identifier>PMID: 17251059</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>angiogenesis ; Animals ; Apoptosis ; DNA, Complementary ; Gene Expression ; gene therapy ; Genetic Therapy ; heart failure ; Heart Failure - etiology ; Heart Failure - physiopathology ; Immunohistochemistry ; Male ; Muscle Cells ; Myocardial Infarction ; Myocardial Ischemia ; Myocardium - cytology ; Myocardium - metabolism ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; vascular endothelial growth factors</subject><ispartof>European journal of heart failure, 2007-04, Vol.9 (4), p.343-351</ispartof><rights>2007 European Society of Cardiology 2007</rights><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © 2007 the Authors</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5117-db7dc627540470f558259ca3b53ae38c2b5eea60d1e901f4902aada9755c52f33</citedby><cites>FETCH-LOGICAL-c5117-db7dc627540470f558259ca3b53ae38c2b5eea60d1e901f4902aada9755c52f33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.ejheart.2006.10.007$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2Fj.ejheart.2006.10.007$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17251059$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruixing, Yin</creatorcontrib><creatorcontrib>Dezhai, Yang</creatorcontrib><creatorcontrib>Hai, Wu</creatorcontrib><creatorcontrib>Kai, Huang</creatorcontrib><creatorcontrib>Xianghong, Wu</creatorcontrib><creatorcontrib>Yuming, Chen</creatorcontrib><title>Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis</title><title>European journal of heart failure</title><addtitle>European Journal of Heart Failure</addtitle><description>Background: Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. Aim: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Methods: Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection. Results: Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P&lt;0.05 to 0.01). Apoptotic index in the treated group was less than in the control (P&lt;0.01). Caspase-3 activation and mitochondrial cytochrome c release in the treated group were also lower than in the control (P&lt;0.01). VEGF165 cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium. Conclusion: Intramyocardial injection of VEGF165 cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction.</description><subject>angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>DNA, Complementary</subject><subject>Gene Expression</subject><subject>gene therapy</subject><subject>Genetic Therapy</subject><subject>heart failure</subject><subject>Heart Failure - etiology</subject><subject>Heart Failure - physiopathology</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Muscle Cells</subject><subject>Myocardial Infarction</subject><subject>Myocardial Ischemia</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>vascular endothelial growth factors</subject><issn>1388-9842</issn><issn>1879-0844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFu1DAURSNERUvhE0BescvwHMdxsoRR22nVgpCALi3Heek4JHFqOy3zA_1uEiUCsevK1vO59z75RtE7ChsKNPvYbLDZo3JhkwBk02wDIF5EJzQXRQx5mr6c7izP4yJPk-PotfcNABUAyavomIqEU-DFSfR02QenuoPVylVGtcT0DepgbE9sTR6U12OrHMG-smGP7UzcOfsY9qRWOlhH7rBHYrrB2Qf0ZHHRZEBXW9epXiNRfTW57k1pwgrYOe8QpqfBDsF6499ER7VqPb5dz9Pox_nZ9-0uvv56cbn9dB1rTqmIq1JUOksETyEVUHOeJ7zQipWcKWS5TkqOqDKoKBZA67SARKlKFYJzzZOasdPow-I77Xs_og-yM15j26oe7eilAAZM0HwC-QJqZ713WMvBmU65g6Qg5wJkI9cC5FzAPJ4KmHTv14Cx7LD6p1p_fAI-L8CjafHwPFd5drU7_z8FFhM7Ds9eLF4kxgf8_Vek3C-ZCSa4vP1yIW9S-m1Ld7fyJ_sDLau7KQ</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Ruixing, Yin</creator><creator>Dezhai, Yang</creator><creator>Hai, Wu</creator><creator>Kai, Huang</creator><creator>Xianghong, Wu</creator><creator>Yuming, Chen</creator><general>Blackwell Publishing Ltd</general><general>Elsevier</general><scope>BSCLL</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>200704</creationdate><title>Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis</title><author>Ruixing, Yin ; Dezhai, Yang ; Hai, Wu ; Kai, Huang ; Xianghong, Wu ; Yuming, Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5117-db7dc627540470f558259ca3b53ae38c2b5eea60d1e901f4902aada9755c52f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>DNA, Complementary</topic><topic>Gene Expression</topic><topic>gene therapy</topic><topic>Genetic Therapy</topic><topic>heart failure</topic><topic>Heart Failure - etiology</topic><topic>Heart Failure - physiopathology</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Muscle Cells</topic><topic>Myocardial Infarction</topic><topic>Myocardial Ischemia</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>vascular endothelial growth factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruixing, Yin</creatorcontrib><creatorcontrib>Dezhai, Yang</creatorcontrib><creatorcontrib>Hai, Wu</creatorcontrib><creatorcontrib>Kai, Huang</creatorcontrib><creatorcontrib>Xianghong, Wu</creatorcontrib><creatorcontrib>Yuming, Chen</creatorcontrib><collection>Istex</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>European journal of heart failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruixing, Yin</au><au>Dezhai, Yang</au><au>Hai, Wu</au><au>Kai, Huang</au><au>Xianghong, Wu</au><au>Yuming, Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis</atitle><jtitle>European journal of heart failure</jtitle><addtitle>European Journal of Heart Failure</addtitle><date>2007-04</date><risdate>2007</risdate><volume>9</volume><issue>4</issue><spage>343</spage><epage>351</epage><pages>343-351</pages><issn>1388-9842</issn><eissn>1879-0844</eissn><abstract>Background: Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known. Aim: To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Methods: Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection. Results: Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P&lt;0.05 to 0.01). Apoptotic index in the treated group was less than in the control (P&lt;0.01). Caspase-3 activation and mitochondrial cytochrome c release in the treated group were also lower than in the control (P&lt;0.01). VEGF165 cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium. Conclusion: Intramyocardial injection of VEGF165 cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>17251059</pmid><doi>10.1016/j.ejheart.2006.10.007</doi><tpages>9</tpages></addata></record>
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subjects angiogenesis
Animals
Apoptosis
DNA, Complementary
Gene Expression
gene therapy
Genetic Therapy
heart failure
Heart Failure - etiology
Heart Failure - physiopathology
Immunohistochemistry
Male
Muscle Cells
Myocardial Infarction
Myocardial Ischemia
Myocardium - cytology
Myocardium - metabolism
Rats
Rats, Sprague-Dawley
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
vascular endothelial growth factors
title Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis
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