|
Michio Otsuki
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor and Division head |
|
| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Favine/CCDC3 deficiency accelerated atherosclerosis and thrombus formation is associated with decreased MEF2C-KLF2 pathway. |
| Journal | Formal name：iScience Abbreviation：iScience ISSN code：25890042/25890042 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 25(11),pp.105252 |
| Author and coauthor | Kobayashi Sachiko, Kita Shunbun, Okuzaki Daisuke, Fujishima Yuya, Otsuki Michio, Kato Hisashi, Nishizawa Yasuko, Miyashita Kazuya, Yokoyama Chieko, Fukuhara Atsunori, Morii Eiichi, Shimomura Iichiro |
| Publication date | 2022/11 |
| Summary | 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 |