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

Abstract

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.