ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Silencing of ceramide synthase 2 in hepatocytes modulates plasma ceramide biomarkers predictive of cardiovascular death.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- LipiDecipher: A Structure-Oriented Analytical Framework for Interpretable Clinical Lipidomics.Metabolites · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Sex-specific lipidomic signatures in aortic valve disease reflect differential fibro-calcific progression.Nature communications · 2025Article
- Ceramides as Biomarkers of Cardiovascular Diseases and Heart Failure.Current heart failure reports · 2024Review
- Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.Integrative medicine research · 2024Article
- The effects of restraint stress on ceramide metabolism disorders in the rat liver: the role of CerS6 in hepatocyte injury.Lipids in health and disease · 2024Article
- Sphingolipids and metabolic disease: Will the real killer please stand up?Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Identification of Five Hub Genes Based on Single-Cell RNA Sequencing Data and Network Pharmacology in Patients With Acute Myocardial Infarction.Frontiers in public health · 2022Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 in liver. Intriguingly, we discover that the hepatocyte-specific antisense oligonucleotide also triggers a parallel modulation of blood plasma ceramides, revealing that the biomarkers predictive of cardiovascular death are governed by ceramide biosynthesis in hepatocytes. Our work showcases a generic therapeutic framework for targeting components of the ceramide enzymatic machinery to disentangle their roles in disease causality and to explore their utility for treatment of cardiometabolic disorders.
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