{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schmidt S"],"funding":["Danish Council for Independent Research","Strategiske Forskningsråd","VILLUM Center for Bioanalytical Sciences","Syddansk Universitet","Seventh Framework Programme","European Commission","Lundbeckfonden"],"pagination":["1661-1674"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9077316"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(4)"],"pubmed_abstract":["Emerging clinical data show that three ceramide molecules, Cer d18:1/16:0, Cer d18:1/24:1, and Cer d18:1/24:0, are biomarkers of a fatal outcome in patients with cardiovascular disease. This finding raises basic questions about their metabolic origin, their contribution to disease pathogenesis, and the utility of targeting the underlying enzymatic machinery for treatment of cardiometabolic disorders. Here, we outline the development of a potent N-acetylgalactosamine-conjugated antisense oligonucleotide engineered to silence ceramide synthase 2 specifically in hepatocytes in vivo. We demonstrate that this compound reduces the ceramide synthase 2 mRNA level and that this translates into efficient lowering of protein expression and activity as well as Cer d18:1/24:1 and Cer d18:1/24:0 levels "],"journal":["Molecular therapy : the journal of the American Society of Gene Therapy"],"pubmed_title":["Silencing of ceramide synthase 2 in hepatocytes modulates plasma ceramide biomarkers predictive of cardiovascular death."],"pmcid":["PMC9077316"],"funding_grant_id":["11-116196","SDU2020","HEALTH-F2-2013-602222","FP7-2007-2013","VKR023179","R54-A5858"],"pubmed_authors":["Overup C","Sprenger RR","Schmidt S","Gallego SF","Albæk N","Zelnik ID","Lindholm MW","Ejsing CS","Kovalchuk S","Futerman AH","Jensen ON","Pewzner-Jung Y"],"additional_accession":[]},"is_claimable":false,"name":"Silencing of ceramide synthase 2 in hepatocytes modulates plasma ceramide biomarkers predictive of cardiovascular death.","description":"Emerging clinical data show that three ceramide molecules, Cer d18:1/16:0, Cer d18:1/24:1, and Cer d18:1/24:0, are biomarkers of a fatal outcome in patients with cardiovascular disease. This finding raises basic questions about their metabolic origin, their contribution to disease pathogenesis, and the utility of targeting the underlying enzymatic machinery for treatment of cardiometabolic disorders. Here, we outline the development of a potent N-acetylgalactosamine-conjugated antisense oligonucleotide engineered to silence ceramide synthase 2 specifically in hepatocytes in vivo. We demonstrate that this compound reduces the ceramide synthase 2 mRNA level and that this translates into efficient lowering of protein expression and activity as well as Cer d18:1/24:1 and Cer d18:1/24:0 levels ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-09T22:19:43.728Z","creation":"2025-02-19T02:38:11.816Z"},"accession":"S-EPMC9077316","cross_references":{"pubmed":["34400330"],"doi":["10.1016/j.ymthe.2021.08.021"]}}