Author + information
- 1Department of Cardiology, China-Japan Friendship Hospital, Peking Union Medical College
- 2Department of Cardiology, China-Japan Friendship Hospital
- 3Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Perking University
Aortic dissection, as a life-threatening cardiovascular disease, is characterized by remodeling of extracellular matrix (ECM) and inflammatory response. ADAMTS1 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1) is able to degrade ECM proteins versican and aggrecan in blood vessels and also is an inflammation-related protein. Previous research revealed that ADAMTS1 is closely associated with aortic dissection development, but whether it contributes to physiopathology of aortic dissection remains unknown.
We created ADAMTS1 floxed mice and whole-body tamoxifen-inducible ADAMTS1 knockout mice (ADAMTS1 flox/flox Ubc-CreERT2+, ADAMTS1 KO) to investigate the functional role of ADAMTS1 in aortic dissection development. Murine aortic dissection were induced in ADAMTS1 flox/flox and ADAMTS1 KO mice by treating with beta-aminopropionitrile (BAPN) for 28 days. ADAMTS1 expression in aorta of BAPN induced mice was evaluated by RT-PCR and Western Blot. The changes of inflammatory cellular infiltration in ADAMTS1 flox/flox and ADAMTS1 KO mice were examined by immunostaining.
We found that ADAMTS1 expression was significantly elevated in the aorta of BAPN treated WT mice. The incidence and rupture rate of aortic dissection in ADAMTS1 KO mice were much lower compared with ADAMTS1 flox/flox mice (45.5% vs. 81.8%, 18.2 vs. 42.4, respectively). Furthermore, immunohistochemical analysis demonstrated that abundance inflammatory cells were accumulated in artery adventitia of ADAMTS1 flox/flox mice in the early stage of aortic dissection induction, which were markedly suppressed in ADAMTS1 KO mice.
In conclusion, ADAMTS1 played a critical role in aortic dissection formation and rupture through regulating the inflammatory response, suggesting ADAMTS1 may be a new therapeutic target for aortic dissection.