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 d...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2860995?pdf=render |
| _version_ | 1811225012799012864 |
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| author | Shirley S Mihardja Dongwei Gao Richard E Sievers Qizhi Fang Jinjin Feng Jianming Wang Henry F Vanbrocklin James W Larrick Manley Huang Michael Dae Randall J Lee |
| author_facet | Shirley S Mihardja Dongwei Gao Richard E Sievers Qizhi Fang Jinjin Feng Jianming Wang Henry F Vanbrocklin James W Larrick Manley Huang Michael Dae Randall J Lee |
| author_sort | Shirley S Mihardja |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T08:59:49Z |
| format | Article |
| id | doaj.art-cee853b442364cc9a2017f7aa05f2cc6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T08:59:49Z |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cee853b442364cc9a2017f7aa05f2cc62022-12-22T03:39:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1038410.1371/journal.pone.0010384Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.Shirley S MihardjaDongwei GaoRichard E SieversQizhi FangJinjin FengJianming WangHenry F VanbrocklinJames W LarrickManley HuangMichael DaeRandall J LeeThe 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.http://europepmc.org/articles/PMC2860995?pdf=render |
| spellingShingle | Shirley S Mihardja Dongwei Gao Richard E Sievers Qizhi Fang Jinjin Feng Jianming Wang Henry F Vanbrocklin James W Larrick Manley Huang Michael Dae Randall J Lee Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. PLoS ONE |
| title | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. |
| title_full | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. |
| title_fullStr | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. |
| title_full_unstemmed | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. |
| title_short | Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. |
| title_sort | targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction |
| url | http://europepmc.org/articles/PMC2860995?pdf=render |
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