ArticleEuropean heart journal2024
TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation.
Article in European heart journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.
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Who cites it
145 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Vascular Immunometabolism in Atherosclerosis: Emerging Roles of Glycometabolic Reprogramming in Immune and Vascular Cells.Cardiovascular drugs and therapy · 2026Pooled it
- Vascular Immunometabolism in Atherosclerosis: Emerging Roles of Glycometabolic Reprogramming in Immune and Vascular Cells.Cardiovascular drugs and therapy · 2026Pooled it
- MTR4 deficiency attenuates abdominal aortic aneurysm progression through suppressing VSMC senescence via the MTR4-RAP1a axis.iScience · 2026Article
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Radiotherapy-Induced Side Effects: Epidemiology, Pathogenesis, Prevention and Treatments.MedComm · 2026Review
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching.Cardiovascular drugs and therapy · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Hypertensive mt. tRNARedox biology · 2026Article
- MCL1 Promotes Endothelial Senescence and Atherosclerosis via Glycolytic Reprogramming-Induced H4K12 Lactylation.International journal of molecular sciences · 2026Article
- USP5 Stabilizes TGFBR1 to Drive Vascular Smooth Muscle Cell Senescence and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TRF2 Recovers Ischemic Postconditioning Cardioprotection in Aged Myocardiocytes by Regulating CSNK2A2 Localization and FUNDC1 Dephosphorylation.Aging cell · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- The pro-tumorigenic functions of cancer-associated adipocytes are dependent on the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1.Signal transduction and targeted therapy · 2026Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
BACKGROUND AND
aimsVascular smooth muscle cell (VSMC) senescence is crucial for the development of atherosclerosis, characterized by metabolic abnormalities. Tumour necrosis factor receptor-associated protein 1 (TRAP1), a metabolic regulator associated with ageing, might be implicated in atherosclerosis. As the role of TRAP1 in atherosclerosis remains elusive, this study aimed to examine the function of TRAP1 in VSMC senescence and atherosclerosis.
methodsTRAP1 expression was measured in the aortic tissues of patients and mice with atherosclerosis using western blot and RT-qPCR. Senescent VSMC models were established by oncogenic Ras, and cellular senescence was evaluated by measuring senescence-associated β-galactosidase expression and other senescence markers. Chromatin immunoprecipitation (ChIP) analysis was performed to explore the potential role of TRAP1 in atherosclerosis.
resultsVSMC-specific TRAP1 deficiency mitigated VSMC senescence and atherosclerosis via metabolic reprogramming. Mechanistically, TRAP1 significantly increased aerobic glycolysis, leading to elevated lactate production. Accumulated lactate promoted histone H4 lysine 12 lactylation (H4K12la) by down-regulating the unique histone lysine delactylase HDAC3. H4K12la was enriched in the senescence-associated secretory phenotype (SASP) promoter, activating SASP transcription and exacerbating VSMC senescence. In VSMC-specific Trap1 knockout ApoeKO mice (ApoeKOTrap1SMCKO), the plaque area, senescence markers, H4K12la, and SASP were reduced. Additionally, pharmacological inhibition and proteolysis-targeting chimera (PROTAC)-mediated TRAP1 degradation effectively attenuated atherosclerosis in vivo.
conclusionsThis study reveals a novel mechanism by which mitonuclear communication orchestrates gene expression in VSMC senescence and atherosclerosis. TRAP1-mediated metabolic reprogramming increases lactate-dependent H4K12la via HDAC3, promoting SASP expression and offering a new therapeutic direction for VSMC senescence and atherosclerosis.
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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.