Plant-Derived Remedy for Repair of Infarcted Heart
Background: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impr...
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| Veröffentlicht in: | PloS one 2009-02, Vol.4 (2), p.e4461-e4461 |
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| creator | Cheng, Lei Chen, Hao Yao, Xinsheng Qi, Guoqing Liu, Hongwei Lee, Kwongman Lee, Kaho Zhang, Jieting Chen, Shihui Lin, Xiaoli Zhao, Wenchao Li, Jiankuan Li, Ming |
| description | Background: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. Methods and Findings: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. Conclusions: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately. |
| doi_str_mv | 10.1371/journal.pone.0004461 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1289785166</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A473409048</galeid><doaj_id>oai_doaj_org_article_48994766b70040baadbd29ec61ced1a6</doaj_id><sourcerecordid>A473409048</sourcerecordid><originalsourceid>FETCH-LOGICAL-c686t-1c351d57b3378426db1b2435a9e156f2408cdaac3e9491113e74899a594e2cea3</originalsourceid><addsrcrecordid>eNqNkl9v0zAUxSMEYmPwDRBUQprEQ4uv7TjxC9I0_qzSpKGN8WrdODetqzQudjKxb49LA2sRDygPtuzfPdf35GTZS2AzEAW8W_khdNjONr6jGWNMSgWPsmPQgk8VZ-Lx3v4oexbjirFclEo9zY5Acw65VscZ_9Ji108_UHB3VE-uaU31_aTxIW036MLEN5N512Cwfbq-IAz98-xJg22kF-N6kt1--vj1_GJ6efV5fn52ObWqVP0UrMihzotKiKKUXNUVVFyKHDVBrhouWWlrRCtISw0AggpZao25lsQtoTjJXu90N62PZhw3GuClLsoclErEfEfUHldmE9waw73x6MyvAx8WJr3X2ZbMVloWSlVFcopViHVVc01WgaUacKv1fuw2VMkDS10fsD0QPbzp3NIs_J3hShS6YEngdBQI_vtAsTdrFy21yV_yQzRKaZFaQwLf_AX-e7bZjlpger7rGp-62vTVtHY2_fPGpfMzWQjJNJNlKnh7UJCYnn70CxxiNPOb6_9nr74dsqd77JKw7ZfRt0PvfBcPQbkDbfAxBmr-mAfMbCP7e06zjawZI5vKXu0b_1A0ZvQhBw16g4vgorm94clIBioFRwnxE3GJ7b4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1289785166</pqid></control><display><type>article</type><title>Plant-Derived Remedy for Repair of Infarcted Heart</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Free E-Journal (出版社公開部分のみ）</source><source>PLoS - Public Library of Sciencem (Open Access)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Cheng, Lei ; Chen, Hao ; Yao, Xinsheng ; Qi, Guoqing ; Liu, Hongwei ; Lee, Kwongman ; Lee, Kaho ; Zhang, Jieting ; Chen, Shihui ; Lin, Xiaoli ; Zhao, Wenchao ; Li, Jiankuan ; Li, Ming</creator><creatorcontrib>Cheng, Lei ; Chen, Hao ; Yao, Xinsheng ; Qi, Guoqing ; Liu, Hongwei ; Lee, Kwongman ; Lee, Kaho ; Zhang, Jieting ; Chen, Shihui ; Lin, Xiaoli ; Zhao, Wenchao ; Li, Jiankuan ; Li, Ming</creatorcontrib><description>Background: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. Methods and Findings: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. Conclusions: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0004461</identifier><identifier>PMID: 19221596</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Animal models ; Animals ; Bioassays ; Biochemistry/Drug Discovery ; Biochemistry/Small Molecule Chemistry ; Bone Morphogenetic Protein 4 - metabolism ; Cancer ; Cardiac Myosins - genetics ; Cardiac Myosins - metabolism ; cardiogenin ; Cardiomyocytes ; Cardiovascular Disorders/Cardiovascular Pharmacology ; Cardiovascular Disorders/Myocardial Infarction ; Cell differentiation ; Cell Differentiation - drug effects ; Cell survival ; Chinese medicine ; Coronary artery ; Coronary artery disease ; Coronary heart disease ; Differentiation ; Echocardiography ; Education ; Embryos ; Gene Expression Profiling ; Genes ; Geum ; Geum japonicum ; Health aspects ; Health sciences ; Heart ; Heart diseases ; Heart transplantation ; herbal medicines ; Humans ; Kinases ; Laboratory animals ; Lymphoma ; Male ; medicinal properties ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - physiology ; Mesenchyme ; Microarray Analysis ; Molecular Structure ; Morphology ; Myocardial Contraction - drug effects ; Myocardial infarction ; Myocardial Infarction - therapy ; Myocardium ; Myocardium - cytology ; Myocardium - metabolism ; Myocardium - pathology ; Myosin Light Chains - genetics ; Myosin Light Chains - metabolism ; plant extracts ; Plant Extracts - pharmacology ; Plant Extracts - therapeutic use ; Plants ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Regeneration ; Regeneration - drug effects ; Rheumatology ; Saponins - pharmacology ; Saponins - therapeutic use ; Signal transduction ; Signal Transduction - physiology ; Signaling ; Stem cell transplantation ; Stem cells ; Survival ; Transplantation</subject><ispartof>PloS one, 2009-02, Vol.4 (2), p.e4461-e4461</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Cheng et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c686t-1c351d57b3378426db1b2435a9e156f2408cdaac3e9491113e74899a594e2cea3</citedby><cites>FETCH-LOGICAL-c686t-1c351d57b3378426db1b2435a9e156f2408cdaac3e9491113e74899a594e2cea3</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/PMC2637970/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637970/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19221596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Lei</creatorcontrib><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Yao, Xinsheng</creatorcontrib><creatorcontrib>Qi, Guoqing</creatorcontrib><creatorcontrib>Liu, Hongwei</creatorcontrib><creatorcontrib>Lee, Kwongman</creatorcontrib><creatorcontrib>Lee, Kaho</creatorcontrib><creatorcontrib>Zhang, Jieting</creatorcontrib><creatorcontrib>Chen, Shihui</creatorcontrib><creatorcontrib>Lin, Xiaoli</creatorcontrib><creatorcontrib>Zhao, Wenchao</creatorcontrib><creatorcontrib>Li, Jiankuan</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><title>Plant-Derived Remedy for Repair of Infarcted Heart</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Background: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. Methods and Findings: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. Conclusions: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Bioassays</subject><subject>Biochemistry/Drug Discovery</subject><subject>Biochemistry/Small Molecule Chemistry</subject><subject>Bone Morphogenetic Protein 4 - metabolism</subject><subject>Cancer</subject><subject>Cardiac Myosins - genetics</subject><subject>Cardiac Myosins - metabolism</subject><subject>cardiogenin</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular Disorders/Cardiovascular Pharmacology</subject><subject>Cardiovascular Disorders/Myocardial Infarction</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell survival</subject><subject>Chinese medicine</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary heart disease</subject><subject>Differentiation</subject><subject>Echocardiography</subject><subject>Education</subject><subject>Embryos</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Geum</subject><subject>Geum japonicum</subject><subject>Health aspects</subject><subject>Health sciences</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart transplantation</subject><subject>herbal medicines</subject><subject>Humans</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Lymphoma</subject><subject>Male</subject><subject>medicinal properties</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Mesenchyme</subject><subject>Microarray Analysis</subject><subject>Molecular Structure</subject><subject>Morphology</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocardium</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Myosin Light Chains - genetics</subject><subject>Myosin Light Chains - metabolism</subject><subject>plant extracts</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Extracts - therapeutic use</subject><subject>Plants</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Regeneration</subject><subject>Regeneration - drug effects</subject><subject>Rheumatology</subject><subject>Saponins - pharmacology</subject><subject>Saponins - therapeutic use</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>Signaling</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Transplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl9v0zAUxSMEYmPwDRBUQprEQ4uv7TjxC9I0_qzSpKGN8WrdODetqzQudjKxb49LA2sRDygPtuzfPdf35GTZS2AzEAW8W_khdNjONr6jGWNMSgWPsmPQgk8VZ-Lx3v4oexbjirFclEo9zY5Acw65VscZ_9Ji108_UHB3VE-uaU31_aTxIW036MLEN5N512Cwfbq-IAz98-xJg22kF-N6kt1--vj1_GJ6efV5fn52ObWqVP0UrMihzotKiKKUXNUVVFyKHDVBrhouWWlrRCtISw0AggpZao25lsQtoTjJXu90N62PZhw3GuClLsoclErEfEfUHldmE9waw73x6MyvAx8WJr3X2ZbMVloWSlVFcopViHVVc01WgaUacKv1fuw2VMkDS10fsD0QPbzp3NIs_J3hShS6YEngdBQI_vtAsTdrFy21yV_yQzRKaZFaQwLf_AX-e7bZjlpger7rGp-62vTVtHY2_fPGpfMzWQjJNJNlKnh7UJCYnn70CxxiNPOb6_9nr74dsqd77JKw7ZfRt0PvfBcPQbkDbfAxBmr-mAfMbCP7e06zjawZI5vKXu0b_1A0ZvQhBw16g4vgorm94clIBioFRwnxE3GJ7b4</recordid><startdate>20090214</startdate><enddate>20090214</enddate><creator>Cheng, Lei</creator><creator>Chen, Hao</creator><creator>Yao, Xinsheng</creator><creator>Qi, Guoqing</creator><creator>Liu, Hongwei</creator><creator>Lee, Kwongman</creator><creator>Lee, Kaho</creator><creator>Zhang, Jieting</creator><creator>Chen, Shihui</creator><creator>Lin, Xiaoli</creator><creator>Zhao, Wenchao</creator><creator>Li, Jiankuan</creator><creator>Li, Ming</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>FBQ</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090214</creationdate><title>Plant-Derived Remedy for Repair of Infarcted Heart</title><author>Cheng, Lei ; Chen, Hao ; Yao, Xinsheng ; Qi, Guoqing ; Liu, Hongwei ; Lee, Kwongman ; Lee, Kaho ; Zhang, Jieting ; Chen, Shihui ; Lin, Xiaoli ; Zhao, Wenchao ; Li, Jiankuan ; Li, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c686t-1c351d57b3378426db1b2435a9e156f2408cdaac3e9491113e74899a594e2cea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Bioassays</topic><topic>Biochemistry/Drug Discovery</topic><topic>Biochemistry/Small Molecule Chemistry</topic><topic>Bone Morphogenetic Protein 4 - metabolism</topic><topic>Cancer</topic><topic>Cardiac Myosins - genetics</topic><topic>Cardiac Myosins - metabolism</topic><topic>cardiogenin</topic><topic>Cardiomyocytes</topic><topic>Cardiovascular Disorders/Cardiovascular Pharmacology</topic><topic>Cardiovascular Disorders/Myocardial Infarction</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell survival</topic><topic>Chinese medicine</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary heart disease</topic><topic>Differentiation</topic><topic>Echocardiography</topic><topic>Education</topic><topic>Embryos</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Geum</topic><topic>Geum japonicum</topic><topic>Health aspects</topic><topic>Health sciences</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart transplantation</topic><topic>herbal medicines</topic><topic>Humans</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Lymphoma</topic><topic>Male</topic><topic>medicinal properties</topic><topic>Mesenchymal Stem Cell Transplantation - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Lei</au><au>Chen, Hao</au><au>Yao, Xinsheng</au><au>Qi, Guoqing</au><au>Liu, Hongwei</au><au>Lee, Kwongman</au><au>Lee, Kaho</au><au>Zhang, Jieting</au><au>Chen, Shihui</au><au>Lin, Xiaoli</au><au>Zhao, Wenchao</au><au>Li, Jiankuan</au><au>Li, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plant-Derived Remedy for Repair of Infarcted Heart</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-02-14</date><risdate>2009</risdate><volume>4</volume><issue>2</issue><spage>e4461</spage><epage>e4461</epage><pages>e4461-e4461</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Background: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. Methods and Findings: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. Conclusions: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19221596</pmid><doi>10.1371/journal.pone.0004461</doi><tpages>e4461</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-02, Vol.4 (2), p.e4461-e4461 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289785166 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Free E-Journal (出版社公開部分のみ）; PLoS - Public Library of Sciencem (Open Access); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Angiogenesis Animal models Animals Bioassays Biochemistry/Drug Discovery Biochemistry/Small Molecule Chemistry Bone Morphogenetic Protein 4 - metabolism Cancer Cardiac Myosins - genetics Cardiac Myosins - metabolism cardiogenin Cardiomyocytes Cardiovascular Disorders/Cardiovascular Pharmacology Cardiovascular Disorders/Myocardial Infarction Cell differentiation Cell Differentiation - drug effects Cell survival Chinese medicine Coronary artery Coronary artery disease Coronary heart disease Differentiation Echocardiography Education Embryos Gene Expression Profiling Genes Geum Geum japonicum Health aspects Health sciences Heart Heart diseases Heart transplantation herbal medicines Humans Kinases Laboratory animals Lymphoma Male medicinal properties Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - physiology Mesenchyme Microarray Analysis Molecular Structure Morphology Myocardial Contraction - drug effects Myocardial infarction Myocardial Infarction - therapy Myocardium Myocardium - cytology Myocardium - metabolism Myocardium - pathology Myosin Light Chains - genetics Myosin Light Chains - metabolism plant extracts Plant Extracts - pharmacology Plant Extracts - therapeutic use Plants Rats Rats, Sprague-Dawley Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Regeneration Regeneration - drug effects Rheumatology Saponins - pharmacology Saponins - therapeutic use Signal transduction Signal Transduction - physiology Signaling Stem cell transplantation Stem cells Survival Transplantation |
| title | Plant-Derived Remedy for Repair of Infarcted Heart |
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