biostudies-literatureKobayashi SNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteJapan Foundation for Applied EnzymologyNational Cancer InstituteNational Institute of Mental HealthNational Institutes of HealthJapan Science and Technology AgencyNational Human Genome Research InstituteMSD Life Science Foundation, Public Interest Incorporated FoundationNational Institute on Drug AbuseJapan Society for the Promotion of Science105252https://www.ebi.ac.uk/biostudies/studies/S-EPMC9587315biostudies-literatureUnknown25(11)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 <i>FAVINE</i> 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 iScienceFavine/CCDC3 deficiency accelerated atherosclerosis and thrombus formation is associated with decreased MEF2C-KLF2 pathway.PMC958731519K0900115H0485316K1955422K086242586076718H02863Kato HShimomura INishizawa YYokoyama CFukuhara AMorii EKobayashi SKita SFujishima YOtsuki MMiyashita KOkuzaki DfalseFavine/CCDC3 deficiency accelerated atherosclerosis and thrombus formation is associated with decreased MEF2C-KLF2 pathway.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 <i>FAVINE</i> 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 2022-01-01T00:00:00Z2022 Nov2026-05-27T23:07:03.224Z2025-02-18T23:29:50.877ZS-EPMC95873153628145510.1016/j.isci.2022.105252