Academic Journal
Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity
| العنوان: | Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity |
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| المؤلفون: | Molla, Md Rasel, Shimizu, Akio, Komeno, Masahiro, Rahman, Nor Idayu A., Soh, Joanne Ern Chi, Nguyen, Le Kim Chi, Khan, Mahbubur Rahman, Tesega, Wondwossen Wale, Chen, Si, Pang, Xiaoling, Tanaka-Okamoto, Miki, Takashima, Noriyuki, Sato, Akira, Suzuki, Tomoaki, Ogita, Hisakazu |
| المساهمون: | MEXT | Japan Society for the Promotion of Science, Takeda Science Foundation, SENSHIN Medical Research Foundation, Uehara Memorial Foundation |
| المصدر: | Communications Biology ; volume 5, issue 1 ; ISSN 2399-3642 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | Whether a small GTPase RhoA plays a role in the pathology of abdominal aortic aneurysm (AAA) has not been determined. We show here that RhoA expression is reduced in human AAA lesions, compared with normal areas. Furthermore, incidence of AAA formation is increased in vascular smooth muscle cell (VSMC)-specific RhoA conditional knockout (cKO) mice. The contractility of the aortic rings and VSMCs from RhoA cKO mice is reduced, and expression of genes related to the VSMC contractility is attenuated by loss of RhoA. RhoA depletion activates the mitogen-activated protein (MAP) kinase signaling, including MAP4K4, in the aorta and VSMCs. Inhibition of MAP4K4 activity by DMX-5804 decreases AAA formation. Set, a binding protein to active RhoA, functions as an activator of MAP4K4 by sequestering PP2A, an inhibitor of MAP4K4, in the absence of RhoA. In conclusion, RhoA counteracts AAA formation through inhibition of MAP4K4 in cooperation with Set. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s42003-022-04042-z |
| الاتاحة: | http://dx.doi.org/10.1038/s42003-022-04042-z https://www.nature.com/articles/s42003-022-04042-z.pdf https://www.nature.com/articles/s42003-022-04042-z |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.83462F82 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s42003-022-04042-z |
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