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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2017 ; 7
(1
): 15857
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Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm
Formation and Rupture
#MMPMID29158532
Shen Y
; Russo V
; Zeglinski MR
; Sellers SL
; Wu Z
; Oram C
; Santacruz S
; Merkulova Y
; Turner C
; Tauh K
; Zhao H
; Bozin T
; Bohunek L
; Zeng H
; Seidman MA
; Bleackley RC
; McManus BM
; Ruoslahti E
; Järvinen TAH
; Granville DJ
Sci Rep
2017[Nov]; 7
(1
): 15857
PMID29158532
show ga
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.