Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture

Yue, Shen, Valerio, Russo, Matthew R, Zeglinski, Stephanie L, Sellers, Zhengguo, Wu, Cameron, Oram, Stephanie, Santacruz, Yulia, Merkulova, Christopher, Turner, Keerit, Tauh, Hongyan, Zhao, Tatjana, Bozin, Lubos, Bohunek, Haishan, Zeng, Michael A, Seidman, R Chris, Bleackley, Bruce M., McManus, Erkki, Ruoslahti, Tero A.H., Järvinen, David J., Granville

Scientific Reports | 2017

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.