ArticleJCI insight2017
Increased de novo ceramide synthesis and accumulation in failing myocardium.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
102 citing papers in PubMed, 130 citations in OpenAlex.
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Article
- A Recovery-Focused Framework for the Management of Cardiogenic Shock.Circulation. Heart failure · 2026Review
- Integrated Myocardial and Plasma Lipidome Across the Human Obesity-Heart Failure Spectrum.Research square · 2026Article
- Integrating untargeted metabolomics and machine learning to reveal an aberration of sphingolipid metabolism in cardiometabolic HFpEF.Diabetology & metabolic syndrome · 2026Article
- Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF.Experimental & molecular medicine · 2026Article
- Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038.International journal of molecular sciences · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Review
- Ceramides as Biomarkers and Pharmacological Targets in Heart Failure Pathophysiology.Biomolecules · 2026Review
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- Activation of IRF3 in cardiomyocytes impairs mitochondrial oxidative function through PGC-1α inhibition and drives heart failure.Nature communications · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Cellular basis of HFpEF: contributions of abnormal lipids.Frontiers in cardiovascular medicine · 2026Review
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025Review
- Plasma Ceramide C24:0/C16:0 Relates to Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.JACC. Advances · 2025Article
- Electrical Remodeling of Pressure Overloaded Rat Heart Is Attenuated if Imposed During Proliferative Cardiac Growth.Acta physiologica (Oxford, England) · 2025Article
- Impact of Nutrition on Sphingolipid-Regulated Physiology: A Review.Molecular nutrition & food research · 2025Review
- Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets.Cardiovascular research · 2025Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed myocardial tissue and serum from patients with severe heart failure (HF) undergoing placement of left ventricular assist devices and controls. Lipidomic analysis revealed increased total and very long-chain ceramides in myocardium and serum of patients with advanced HF. After unloading, these changes showed partial reversibility. Following myocardial infarction (MI), serine palmitoyl transferase (SPT), the rate-limiting enzyme of the de novo pathway of ceramide synthesis, and ceramides were found increased. Blockade of SPT by the specific inhibitor myriocin reduced ceramide accumulation in ischemic cardiomyopathy and decreased C16, C24:1, and C24 ceramides. SPT inhibition also reduced ventricular remodeling, fibrosis, and macrophage content following MI. Further, genetic deletion of the SPTLC2 gene preserved cardiac function following MI. Finally, in vitro studies revealed that changes in ceramide synthesis are linked to hypoxia and inflammation. In conclusion, cardiac ceramides accumulate in the failing myocardium, and increased levels are detectable in circulation. Inhibition of de novo ceramide synthesis reduces cardiac remodeling. Thus, increased de novo ceramide synthesis contributes to progressive pathologic cardiac remodeling and dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.