オオツキ ミチオ   Ootsuki Michio
  大月 道夫
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授・基幹分野長
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Favine/CCDC3 deficiency accelerated atherosclerosis and thrombus formation is associated with decreased MEF2C-KLF2 pathway.
掲載誌名 正式名:iScience
略  称:iScience
ISSNコード:25890042/25890042
掲載区分国外
巻・号・頁 25(11),pp.105252
著者・共著者 Kobayashi Sachiko, Kita Shunbun, Okuzaki Daisuke, Fujishima Yuya, Otsuki Michio, Kato Hisashi, Nishizawa Yasuko, Miyashita Kazuya, Yokoyama Chieko, Fukuhara Atsunori, Morii Eiichi, Shimomura Iichiro
発行年月 2022/11
概要 Currently, no mouse models manifest calcification and thrombus formation, which is frequently associated with human atherosclerosis. We demonstrated that lack of Favine/CCDC3 in apoE knockout mice accelerated atherosclerosis accompanied by large cholesterol crystals and calcification, and also promoted thrombus formation in the left ventricle and arteries. Circulating Favine was detectable in WT mouse plasma. RNA-sequencing analysis of aortae in DKO mice showed similar gene expression patterns of human atherosclerosis with unstable and vulnerable plaques. Importantly, human FAVINE mRNA expressions were lower in atheroma plaque than in adjacent intact aortic tissue and decreased with the progression of atherosclerosis. Pathway analysis of aortae in DKO mice suggested the decrease of the MEF2C-KLF2-mediated transcriptional pathway. Favine insufficiency and its attenuated downstream pathways may increase atherosclerosis progression with calcification and thrombus, which have not previously been fully modeled in experimental animals. Favine and its downstream pathways may have therapeutic potential for atherosclerosis.
DOI 10.1016/j.isci.2022.105252
PMID 36281455