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Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture
Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696466/ https://www.ncbi.nlm.nih.gov/pubmed/29158532 http://dx.doi.org/10.1038/s41598-017-16194-8 |
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author | Shen, Yue Russo, Valerio Zeglinski, Matthew R. Sellers, Stephanie L. Wu, Zhengguo Oram, Cameron Santacruz, Stephanie Merkulova, Yulia Turner, Christopher Tauh, Keerit Zhao, Hongyan Bozin, Tatjana Bohunek, Lubos Zeng, Haishan Seidman, Michael A. Bleackley, R. Chris McManus, Bruce M. Ruoslahti, Erkki Järvinen, Tero A. H. Granville, David J. |
author_facet | Shen, Yue Russo, Valerio Zeglinski, Matthew R. Sellers, Stephanie L. Wu, Zhengguo Oram, Cameron Santacruz, Stephanie Merkulova, Yulia Turner, Christopher Tauh, Keerit Zhao, Hongyan Bozin, Tatjana Bohunek, Lubos Zeng, Haishan Seidman, Michael A. Bleackley, R. Chris McManus, Bruce M. Ruoslahti, Erkki Järvinen, Tero A. H. Granville, David J. |
author_sort | Shen, Yue |
collection | PubMed |
description | Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall. In the present study, the role of systemically-administered CAR-DCN in AAA progression and rupture was assessed in a murine model. Apolipoprotein E knockout (ApoE-KO) mice were infused with angiotensin II (AngII) for 28 days to induce AAA formation. CAR-DCN or vehicle was administrated systemically until day 15. Mortality due to AAA rupture was significantly reduced in CAR-DCN-treated mice compared to controls. Although the prevalence of AAA was similar between vehicle and CAR-DCN groups, the severity of AAA in the CAR-DCN group was significantly reduced. Histological analysis revealed that CAR-DCN treatment significantly increased DCN and collagen levels within the aortic wall as compared to vehicle controls. Taken together, these results suggest that CAR-DCN treatment attenuates the formation and rupture of Ang II-induced AAA in mice by reinforcing the aortic wall. |
format | Online Article Text |
id | pubmed-5696466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56964662017-11-29 Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture Shen, Yue Russo, Valerio Zeglinski, Matthew R. Sellers, Stephanie L. Wu, Zhengguo Oram, Cameron Santacruz, Stephanie Merkulova, Yulia Turner, Christopher Tauh, Keerit Zhao, Hongyan Bozin, Tatjana Bohunek, Lubos Zeng, Haishan Seidman, Michael A. Bleackley, R. Chris McManus, Bruce M. Ruoslahti, Erkki Järvinen, Tero A. H. Granville, David J. Sci Rep Article Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall. In the present study, the role of systemically-administered CAR-DCN in AAA progression and rupture was assessed in a murine model. Apolipoprotein E knockout (ApoE-KO) mice were infused with angiotensin II (AngII) for 28 days to induce AAA formation. CAR-DCN or vehicle was administrated systemically until day 15. Mortality due to AAA rupture was significantly reduced in CAR-DCN-treated mice compared to controls. Although the prevalence of AAA was similar between vehicle and CAR-DCN groups, the severity of AAA in the CAR-DCN group was significantly reduced. Histological analysis revealed that CAR-DCN treatment significantly increased DCN and collagen levels within the aortic wall as compared to vehicle controls. Taken together, these results suggest that CAR-DCN treatment attenuates the formation and rupture of Ang II-induced AAA in mice by reinforcing the aortic wall. Nature Publishing Group UK 2017-11-20 /pmc/articles/PMC5696466/ /pubmed/29158532 http://dx.doi.org/10.1038/s41598-017-16194-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shen, Yue Russo, Valerio Zeglinski, Matthew R. Sellers, Stephanie L. Wu, Zhengguo Oram, Cameron Santacruz, Stephanie Merkulova, Yulia Turner, Christopher Tauh, Keerit Zhao, Hongyan Bozin, Tatjana Bohunek, Lubos Zeng, Haishan Seidman, Michael A. Bleackley, R. Chris McManus, Bruce M. Ruoslahti, Erkki Järvinen, Tero A. H. Granville, David J. Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title | Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title_full | Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title_fullStr | Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title_full_unstemmed | Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title_short | Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture |
title_sort | recombinant decorin fusion protein attenuates murine abdominal aortic aneurysm formation and rupture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696466/ https://www.ncbi.nlm.nih.gov/pubmed/29158532 http://dx.doi.org/10.1038/s41598-017-16194-8 |
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