Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity.

Autor: Molla MR; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Shimizu A; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Komeno M; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Rahman NIA; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Soh JEC; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Nguyen LKC; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Khan MR; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Tesega WW; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Chen S; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan.; Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, China., Pang X; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan.; Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, China., Tanaka-Okamoto M; Department of Molecular Biology, Osaka International Cancer Institute, Osaka, Japan., Takashima N; Division of Cardiovascular Surgery and Thoracic Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan., Sato A; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan., Suzuki T; Division of Cardiovascular Surgery and Thoracic Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan., Ogita H; Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Japan. hogita@belle.shiga-med.ac.jp.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Oct 07; Vol. 5 (1), pp. 1071. Date of Electronic Publication: 2022 Oct 07.
DOI: 10.1038/s42003-022-04042-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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