Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle
Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment mod...
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National Academy of Sciences of the United States of America
2012
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| Online Access: | http://hdl.handle.net/1721.1/71851 https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0003-4255-0492 |
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| author | Jang, Eugene Albadawi, Hassan Watkins, Michael T. Edelman, Elazer R. Baker, Aaron B. Langer, Robert |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Jang, Eugene Albadawi, Hassan Watkins, Michael T. Edelman, Elazer R. Baker, Aaron B. Langer, Robert |
| author_sort | Jang, Eugene |
| collection | MIT |
| description | Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue. |
| first_indexed | 2024-09-23T15:55:55Z |
| format | Article |
| id | mit-1721.1/71851 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:55:55Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences of the United States of America |
| record_format | dspace |
| spelling | mit-1721.1/718512022-10-02T05:07:57Z Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle Jang, Eugene Albadawi, Hassan Watkins, Michael T. Edelman, Elazer R. Baker, Aaron B. Langer, Robert Harvard University--MIT Division of Health Sciences and Technology Edelman, Elazer R. Jang, Eugene Edelman, Elazer R. Langer, Robert Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue. 2012-07-26T19:07:27Z 2012-07-26T19:07:27Z 2012-01 2011-11 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/71851 Jang, E. et al. “Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle.” Proceedings of the National Academy of Sciences 109.5 (2012): 1679–1684. Copyright ©2012 by the National Academy of Sciences https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1117885109 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences of the United States of America PNAS |
| spellingShingle | Jang, Eugene Albadawi, Hassan Watkins, Michael T. Edelman, Elazer R. Baker, Aaron B. Langer, Robert Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title | Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title_full | Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title_fullStr | Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title_full_unstemmed | Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title_short | Syndecan-4 Proteoliposomes Enhance Fibroblast Growth Factor-2 (FGF-2)-induced Proliferation, Migration, and Neovascularization of Ischemic Muscle |
| title_sort | syndecan 4 proteoliposomes enhance fibroblast growth factor 2 fgf 2 induced proliferation migration and neovascularization of ischemic muscle |
| url | http://hdl.handle.net/1721.1/71851 https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0003-4255-0492 |
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