ArticleJournal of molecular and cellular cardiology2019
HDAC inhibition induces autophagy and mitochondrial biogenesis to maintain mitochondrial homeostasis during cardiac ischemia/reperfusion injury.
Article in Journal of molecular and cellular cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 96 citations in OpenAlex.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Osimertinib-induced cardiotoxicity is driven by HDAC-dependent epigenetic repression and rescued by vorinostat.Signal transduction and targeted therapy · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Mitochondrial signatures of infant mesenchymal stem cells predict child adiposity: The Healthy Start Study.Research square · 2026Article
- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.bioRxiv : the preprint server for biology · 2026Article
- A multimodal vision knowledge graph of cardiovascular disease.Nature cardiovascular research · 2026Article
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Advances in mitochondria-nucleus crosstalk in septic cardiomyopathy.Cell biology and toxicology · 2025Review
- Mitochondrial DNA Dysfunction in Cardiovascular Diseases: A Novel Therapeutic Target.Antioxidants (Basel, Switzerland) · 2025Review
- Mitochondrial Quality Control in Health and Disease.MedComm · 2025Review
- Role of autophagy in neurotoxic protein's clearance following post-ischemic stroke: where we are and what we know?Molecular brain · 2025Review
- Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment.Cardiovascular diabetology · 2025Review
- Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs.Proteomics · 2025Article
- Disruption of mitochondrial DNA integrity in cardiomyocyte injury upon ischemia/reperfusion.Genes & diseases · 2025Review
- Mitochondria and myocardial ischemia/reperfusion injury: Effects of Chinese herbal medicine and the underlying mechanisms.Journal of pharmaceutical analysis · 2025Review
- Leptin drives glucose metabolism to promote cardiac protection via OPA1-mediated HDAC5 translocation and Glut4 transcription.Functional & integrative genomics · 2025Article
- Autophagy in the lung: guardian of homeostasis or driver of disease.Autophagy reports · 2025Review
- Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches.Results and problems in cell differentiation · 2025Review
- Inhibition of MARK4 Promotes Mitochondrial Biogenesis by Inducing the Phosphorylation of AMPKα to Reduce Myocardial Damage in Rats With Myocardial Infarction.Cardiology research and practice · 2025Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsThe FDA-approved histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA, Vorinostat) has been shown to induce cardiomyocyte autophagy and blunt ischemia/reperfusion (I/R) injury when administered at the time of reperfusion. However, the precise mechanisms underlying the cardioprotective activity of SAHA are unknown. Mitochondrial dysfunction and oxidative damage are major contributors to myocardial apoptosis during I/R injury. We hypothesize that SAHA protects the myocardium by maintaining mitochondrial homeostasis and reducing reactive oxygen species (ROS) production during I/R injury.
methodsMouse and cultured cardiomyocytes (neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes) I/R models were used to investigate the effects of SAHA on mitochondria. ATG7 knockout mice, ATG7 knockdown by siRNA and PGC-1α knockdown by adenovirus in cardiomyocytes were used to test the dependency of autophagy and PGC-1α-mediated mitochondrial biogenesis respectively.
resultsIntact and total mitochondrial DNA (mtDNA) content and mitochondrial mass were significantly increased in cardiomyocytes by SAHA pretreatment before simulated I/R. In vivo, I/R induced >50% loss of mtDNA content in the border zones of mouse hearts, but SAHA pretreatment and reperfusion treatment alone reverted mtDNA content and mitochondrial mass to control levels. Moreover, pretreatment of cardiomyocytes with SAHA resulted in a 4-fold decrease in I/R-induced loss of mitochondrial membrane potential and a 25%-40% reduction in cytosolic ROS levels. However, loss-of-function of ATG7 in cardiomyocytes or mouse myocardium abolished the protective effects of SAHA on ROS levels, mitochondrial membrane potential, mtDNA levels, and mitochondrial mass. Lastly, PGC-1α gene expression was induced by SAHA in NRVMs and mouse heart subjected to I/R, and loss of PGC-1α abrogated SAHA's mitochondrial protective effects in cardiomyocytes.
conclusionsSAHA prevents I/R induced-mitochondrial dysfunction and loss, and reduces myocardial ROS production when given before or after the ischemia. The protective effects of SAHA on mitochondria are dependent on autophagy and PGC-1α-mediated mitochondrial biogenesis.
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