オクヤマ　ミチヒロ   Michihiro Okuyama   奥山　倫弘    所属   川崎医科大学  医学部 臨床医学　心臓血管外科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Mst1/2 Kinases Inhibitor, XMU-MP-1, Attenuates Angiotensin II-Induced Ascending Aortic Expansion in Hypercholesterolemic Mice.
掲載誌名	正式名：Circulation reports 略　 称：Circ Rep ISSNコード：24340790/24340790
掲載区分	国外
巻・号・頁	3(5),pp.259-266
国際共著	国際共著
著者・共著者	Michihiro Okuyama, Weihua Jiang, Lihua Yang, Venkateswaran Subramanian
担当区分	筆頭著者
発行年月	2021/04
概要	Background: Ascending and abdominal aortic aneurysms (AAs) are asymptomatic, permanent dilations of the aorta with surgical intervention as the currently available therapy. Hippo-Yap signaling cascade plays a critical role in stem cell self-renewal, tissue regeneration and organ size control. By using XMU-MP-1, a pharmacological inhibitor of the key component of Hippo-Yap signaling, MST1/2, we examined the functional contribution of Hippo-Yap in the development of AAs in Angiotensin II (AngII)-infused hypercholesterolemic mice. Methods and Results: MST, p-MST, p-YAP, p-MOB and TAZ proteins in AngII-infused ascending and abdominal aortas were assessed by immunohistochemical and western blot analyses. To examine the effect of MST1/2 inhibition on AAs, western diet-fed low density lipoprotein (LDL) receptor -/- mice infused with AngII were administered with either vehicle or XMU-MP-1 for 5 weeks. Hippo-YAP signaling proteins were significantly elevated in AngII infused ascending and abdominal aortas. XMU-MP-1 administration resulted in the attenuation of AngII-induced ascending AAs without influencing abdominal AAs and aortic atherosclerosis. Inhibition of Hippo-YAP signaling also resulted in the suppression of AngII-induced matrix metalloproteinase 2 (MMP2) activity, macrophage accumulation, aortic medial hypertrophy and elastin breaks in the ascending aorta. Conclusions: The present study demonstrates a pivotal role for the Hippo-YAP signaling pathway in AngII-induced ascending AA development.
DOI	10.1253/circrep.CR-20-0104
PMID	34007939