ArticleEMBO molecular medicine2021
Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06922994 (Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression), which is not on this map. Cited by 28 papers.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression
Who cites it
28 citing papers in PubMed, 30 citations in OpenAlex.
- Lipid Metabolism as a Therapeutic Target in Arrhythmogenic Cardiomyopathy: Emerging Therapeutic Implications of Lipid-Lowering Therapy.Reviews in cardiovascular medicine · 2026Review
- Review
- Review
- Acute binge alcohol increases risk of arrhythmias and myocardial fibrosis in a mouse model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Article
- Maintenance of Energy Metabolism Is an Integral Part of Plakophilin-2 and Desmosome Functions.JACC. Basic to translational science · 2025Article
- Epigenetic Drugs Splitomicin, Suberohydroxamic Acid, CPTH6, BVT-948, and PBIT Moderate Fibro-Fatty Development in Arrhythmogenic Cardiomyopathy.Biomolecules · 2025Article
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- The Right Approach: Power of Biomarkers in the Assessment and Management of Right Ventricular Dysfunction.International journal of molecular sciences · 2025Review
- Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases.International journal of molecular sciences · 2025Review
- Statin effect on arrhythmogenic cardiomyopathy disease progression (SEARCH): Randomized clinical study protocol.PloS one · 2025Article
- Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging.Science advances · 2024Article
- Cardiomyocyte and stromal cell cross-talk influences the pathogenesis of arrhythmogenic cardiomyopathy: a multi-level analysis uncovers DLK1-NOTCH pathway role in fibro-adipose remodelling.Cell death discovery · 2024Article
- Role of miRNA-mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy.Biomedicines · 2024Article
- High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy.Nutrients · 2024Article
- Cytotoxicity, Antiadipogenic, Low-Density Lipoprotein Oxidation Inhibitory Activities, and Acute Toxicity Study ofTheScientificWorldJournal · 2024Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Patient-specific primary and pluripotent stem cell-derived stromal cells recapitulate key aspects of arrhythmogenic cardiomyopathy.Scientific reports · 2023Article
- Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.Nature communications · 2023Article
- Omics Analyses of Stromal Cells from ACM Patients Reveal Alterations in Chromatin Organization and Mitochondrial Homeostasis.International journal of molecular sciences · 2023Article
- Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes.Computational and structural biotechnology journal · 2023Article
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Authors and funding
32 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro-adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low-density lipoprotein (oxLDL)-dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient-derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock-out mice through high-fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies.
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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.