scholarly journals Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin

2008 ◽  
Vol 16 (11) ◽  
pp. 1413-1420 ◽  
Author(s):  
Y. Luan ◽  
L. Kong ◽  
D.R. Howell ◽  
K. Ilalov ◽  
M. Fajardo ◽  
...  

2015 ◽  
Vol 11 (999) ◽  
pp. 1-1
Author(s):  
Maurizio Benucci ◽  
Francesca Meacci ◽  
Mariangela Manfredi ◽  
Francesca Gobbi ◽  
Maria Infantino ◽  
...  


2008 ◽  
Vol 70 (9) ◽  
pp. 915-921 ◽  
Author(s):  
Koh ARAI ◽  
Masaaki TAGAMI ◽  
Takashi HATAZOE ◽  
Eikoh NISHIMATSU ◽  
Yuri SHIMIZU ◽  
...  


Cell Research ◽  
2021 ◽  
Author(s):  
Yi Fu ◽  
Yaqian Huang ◽  
Zhao Yang ◽  
Yufei Chen ◽  
Jingang Zheng ◽  
...  

AbstractCompelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. COMP deficiency results in activation of AT1a-β-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion. AAAs in COMP–/– or ApoE–/– mice are rescued by AT1a or β-arrestin-2 deficiency, or the application of a peptidomimetic mimicking the AT1-binding motif of COMP. Explorations of the endogenous biased antagonism of AT1 receptor or other GPCRs may reveal novel therapeutic strategies for cardiovascular diseases.





2001 ◽  
Vol 9 (7) ◽  
pp. 612-618 ◽  
Author(s):  
V. Vilı́m ◽  
R. Vytášek ◽  
M. Olejárová ◽  
S. Macháček ◽  
J. Gatterová ◽  
...  


2008 ◽  
Vol 16 ◽  
pp. S53-S54
Author(s):  
M. Scarpellini ◽  
A. Lurati ◽  
K. Re ◽  
M. Marrazza


1997 ◽  
Vol 272 (22) ◽  
pp. 14120-14126 ◽  
Author(s):  
Joseph Zaia ◽  
Raymond E. Boynton ◽  
Angela McIntosh ◽  
Daniel R. Marshak ◽  
Henric Olsson ◽  
...  


2011 ◽  
Vol 179 (4) ◽  
pp. 1951-1960 ◽  
Author(s):  
Shigeki Inui ◽  
Fumie Shono ◽  
Takeshi Nakajima ◽  
Ko Hosokawa ◽  
Satoshi Itami


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