Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction
The extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair. Four peptides, 2 derived from fibronectin and 2...
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| Veröffentlicht in: | PloS one 2010-04, Vol.5 (4), p.e10384 |
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| creator | Mihardja, Shirley S Gao, Dongwei Sievers, Richard E Fang, Qizhi Feng, Jinjin Wang, Jianming Vanbrocklin, Henry F Larrick, James W Huang, Manley Dae, Michael Lee, Randall J |
| description | The extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.
Four peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.
We demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology. |
| doi_str_mv | 10.1371/journal.pone.0010384 |
| format | Article |
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Four peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.
We demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0010384</identifier><identifier>PMID: 20442783</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Animals ; Antibodies ; Antibodies - administration & dosage ; Antibodies - therapeutic use ; Bioengineering ; Biotechnology/Bioengineering ; Biotechnology/Small Molecule Chemistry ; Cardiomyopathy ; Cardiovascular Disorders/Myocardial Infarction ; Cell activation ; Cell adhesion ; Cell adhesion & migration ; Cell growth ; Cells (Biology) ; Collagen ; Collagen (type IV) ; Collagen Type IV - chemistry ; Drug Delivery Systems - methods ; Endothelial cells ; Extracellular matrix ; Extracellular Matrix - physiology ; Fibroblasts ; Fibronectin ; Fibronectins ; Fibronectins - chemistry ; Geometry ; Heart attack ; Heart attacks ; Immunoconjugates - therapeutic use ; In vivo methods and tests ; Ischemia ; Maintenance ; Matrix protein ; Medicine ; Muscle proteins ; Myocardial infarction ; Myocardial Infarction - drug therapy ; Myocardial Infarction - pathology ; Myocardial Reperfusion Injury - drug therapy ; Myocardium ; Myosin ; Myosin Heavy Chains - immunology ; Neovascularization ; Neovascularization, Physiologic - drug effects ; Peptide Fragments - administration & dosage ; Peptide Fragments - therapeutic use ; Peptides ; Proteins ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Reperfusion ; Studies ; Tissue engineering ; Vascularization</subject><ispartof>PloS one, 2010-04, Vol.5 (4), p.e10384</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Mihardja et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (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>Mihardja et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-6556536b97ec5745d0e076b2d5804f9c9b120c0337619d254bea2dc4d1e1120b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860995/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860995/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23855,27913,27914,53780,53782,79359,79360</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20442783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Egles, Christophe</contributor><creatorcontrib>Mihardja, Shirley S</creatorcontrib><creatorcontrib>Gao, Dongwei</creatorcontrib><creatorcontrib>Sievers, Richard E</creatorcontrib><creatorcontrib>Fang, Qizhi</creatorcontrib><creatorcontrib>Feng, Jinjin</creatorcontrib><creatorcontrib>Wang, Jianming</creatorcontrib><creatorcontrib>Vanbrocklin, Henry F</creatorcontrib><creatorcontrib>Larrick, James W</creatorcontrib><creatorcontrib>Huang, Manley</creatorcontrib><creatorcontrib>Dae, Michael</creatorcontrib><creatorcontrib>Lee, Randall J</creatorcontrib><title>Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.
Four peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.
We demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - administration & dosage</subject><subject>Antibodies - therapeutic use</subject><subject>Bioengineering</subject><subject>Biotechnology/Bioengineering</subject><subject>Biotechnology/Small Molecule Chemistry</subject><subject>Cardiomyopathy</subject><subject>Cardiovascular Disorders/Myocardial Infarction</subject><subject>Cell activation</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cells (Biology)</subject><subject>Collagen</subject><subject>Collagen (type IV)</subject><subject>Collagen Type IV - chemistry</subject><subject>Drug Delivery Systems - methods</subject><subject>Endothelial cells</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - 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therapeutic use</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration</subject><subject>Reperfusion</subject><subject>Studies</subject><subject>Tissue engineering</subject><subject>Vascularization</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7of-A9GCsODFjPlucyMsix8DCwu6ehtO03QmQ9qMSTvs-utNne4yBQXJRcI5z3kT3rxZ9gqjJaYFfr_1Q-jALXe-M0uEMKIle5KdYknJQhBEnx6dT7KzGLcIcVoK8Tw7IYgxUpT0NNvfQlib3tS57fK93fvc3PUBtHFucBDyFvpg7_LGh3Syvst3wbe-NzHvjN9D1CNlfx16SQLy4GvT9XmbNpf7Jm_vvYZQW3Cp30DQI_oie9aAi-bltJ9n3z99vL36sri--by6urxeaCFxvxCcC05FJQujecF4jQwqREVqXiLWSC0rTJBGlBYCy5pwVhkgtWY1Njh1KnqevTno7pyParIsKkxKyRiljCRidSBqD1u1C7aFcK88WPWn4MNaQeitdkZpY0pOq2QdFUxrCQThoikAEG-I1iJpfZhuG6rW1Dr5EMDNROedzm7U2u8VKQWSkieBt5NA8D8HE_t_PHmi1pBelUz144-1Nmp1yQpaSsHKIlHLv1Bp1aa1OoWmsak-G3g3G0hMn8KwhiFGtfr29f_Zmx9z9uKI3Rhw_SZ6N4w5iHOQHUAdfIzBNI_OYaTGzD-4ocbMqynzaez1seuPQw8hp78Bgoz-bQ</recordid><startdate>20100428</startdate><enddate>20100428</enddate><creator>Mihardja, Shirley S</creator><creator>Gao, Dongwei</creator><creator>Sievers, Richard E</creator><creator>Fang, Qizhi</creator><creator>Feng, Jinjin</creator><creator>Wang, Jianming</creator><creator>Vanbrocklin, Henry F</creator><creator>Larrick, James W</creator><creator>Huang, Manley</creator><creator>Dae, Michael</creator><creator>Lee, Randall J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100428</creationdate><title>Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction</title><author>Mihardja, Shirley S ; Gao, Dongwei ; Sievers, Richard E ; Fang, Qizhi ; Feng, Jinjin ; Wang, Jianming ; Vanbrocklin, Henry F ; Larrick, James W ; Huang, Manley ; Dae, Michael ; Lee, Randall J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-6556536b97ec5745d0e076b2d5804f9c9b120c0337619d254bea2dc4d1e1120b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - administration & dosage</topic><topic>Antibodies - therapeutic use</topic><topic>Bioengineering</topic><topic>Biotechnology/Bioengineering</topic><topic>Biotechnology/Small Molecule Chemistry</topic><topic>Cardiomyopathy</topic><topic>Cardiovascular Disorders/Myocardial Infarction</topic><topic>Cell activation</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cells (Biology)</topic><topic>Collagen</topic><topic>Collagen (type IV)</topic><topic>Collagen Type IV - chemistry</topic><topic>Drug Delivery Systems - methods</topic><topic>Endothelial cells</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - physiology</topic><topic>Fibroblasts</topic><topic>Fibronectin</topic><topic>Fibronectins</topic><topic>Fibronectins - chemistry</topic><topic>Geometry</topic><topic>Heart attack</topic><topic>Heart attacks</topic><topic>Immunoconjugates - therapeutic use</topic><topic>In vivo methods and tests</topic><topic>Ischemia</topic><topic>Maintenance</topic><topic>Matrix protein</topic><topic>Medicine</topic><topic>Muscle proteins</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - 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We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.
Four peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.
We demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20442783</pmid><doi>10.1371/journal.pone.0010384</doi><tpages>e10384</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-04, Vol.5 (4), p.e10384 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289443342 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Angiogenesis Animals Antibodies Antibodies - administration & dosage Antibodies - therapeutic use Bioengineering Biotechnology/Bioengineering Biotechnology/Small Molecule Chemistry Cardiomyopathy Cardiovascular Disorders/Myocardial Infarction Cell activation Cell adhesion Cell adhesion & migration Cell growth Cells (Biology) Collagen Collagen (type IV) Collagen Type IV - chemistry Drug Delivery Systems - methods Endothelial cells Extracellular matrix Extracellular Matrix - physiology Fibroblasts Fibronectin Fibronectins Fibronectins - chemistry Geometry Heart attack Heart attacks Immunoconjugates - therapeutic use In vivo methods and tests Ischemia Maintenance Matrix protein Medicine Muscle proteins Myocardial infarction Myocardial Infarction - drug therapy Myocardial Infarction - pathology Myocardial Reperfusion Injury - drug therapy Myocardium Myosin Myosin Heavy Chains - immunology Neovascularization Neovascularization, Physiologic - drug effects Peptide Fragments - administration & dosage Peptide Fragments - therapeutic use Peptides Proteins Rats Rats, Sprague-Dawley Regeneration Reperfusion Studies Tissue engineering Vascularization |
| title | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T08%3A46%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targeted%20in%20vivo%20extracellular%20matrix%20formation%20promotes%20neovascularization%20in%20a%20rodent%20model%20of%20myocardial%20infarction&rft.jtitle=PloS%20one&rft.au=Mihardja,%20Shirley%20S&rft.date=2010-04-28&rft.volume=5&rft.issue=4&rft.spage=e10384&rft.pages=e10384-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0010384&rft_dat=%3Cgale_plos_%3EA473896487%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289443342&rft_id=info:pmid/20442783&rft_galeid=A473896487&rft_doaj_id=oai_doaj_org_article_cee853b442364cc9a2017f7aa05f2cc6&rfr_iscdi=true |