Abstract 487: Systemic Administration of Target-Seeking, Vessel Penetrating Recombinant Decorin Fusion Protein, Car-DCN, Reduces Severity of Abdominal Aortic Aneurysm in Mice

Autor: Yue (Steve) Shen, Valerio Russo, Matthew Zeglinski, Stephanie Sellers, Zhengguo Wu, Cameron Oram, Stephanie Santacruz, Yulia Merkulova, Christopher Turner, Keerit Tauh, Hongyan Zhao, Tatjana Bozin, Lubos Bohunek, Haishan Zeng, Michael Seidman, Bruce McManus, R C Bleackley, Erkki Ruoslahti, Tero A Järvinen, David Granville
Rok vydání: 2017
Předmět:
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 37
ISSN: 1524-4636
1079-5642
DOI: 10.1161/atvb.37.suppl_1.487
Popis: Objective: Decorin (DCN) is a small leucine-rich proteoglycan that mediates collagen fibrollogenesis, organization, and tensile strength. DCN is reduced in abdominal aortic aneurysm (AAA) through a Granzyme B-dependent mechanism resulting in vessel wall instability and aneurysm formation. A recombinant decorin fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflammatory blood vessels and penetrates deep into the vessel wall. In the present study, we sought to evaluate the role of systemically administered CAR-DCN in AAA progression and rupture rate in a murine model. Approach and Results: To induce aneurysm, apolipoprotein E knockout (ApoE-KO) mice were infused with 28 days of angiotensin II (AngII). CAR-DCN or vehicle was systemically administrated until day 15. We observed a significant increase in the survival of CAR-DCN-treated mice (93%) compared to vehicle controls (60%). Although the incidence of AAA onset was similar between vehicle and CAR-DCN groups, the severity of aneurysm in the CAR-DCN group was significantly reduced. Furthermore, histological analysis revealed that CAR-DCN treatment significantly increased DCN and collagen levels in aortic walls compares to vehicle controls. Conclusions: CAR-DCN administration attenuated the severity of Ang II-induced AAA in mice by reinforcing the vessel wall. CAR-DCN may represent a novel therapeutic strategy to attenuate AAA progression and rupture.
Databáze: OpenAIRE
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