ArticleCardiovascular research2023
Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Chitinase‑3 like‑protein‑1: A potential predictor of cardiovascular disease (Review).Molecular medicine reports · 2024Pooled it
- USP30 senses serine/glycine levels to regulate serine biosynthesis and colorectal tumorigenesis by deubiquitinating FTO.Cell death and differentiation · 2026Article
- SIRT3 deficiency drives alveolar epithelial mitochondrial dysfunction in bronchopulmonary dysplasia via PDHA1 hyperacetylation.iScience · 2026Article
- Emerging Roles for Metabolism in Myocardial Inflammation During Heart Failure.Immunological reviews · 2026Review
- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- Discovery of sulfonyl benzoic acid derivatives with joint TGR5-agonist and FXR-antagonist activity for myocardial ischemia/reperfusion injury protection.Acta pharmaceutica Sinica. B · 2026Article
- Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function.Communications biology · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- PDK4 acts via hippo signaling to inhibit ferroptosis and reduce gemcitabine sensitivity in pancreatic cancer.Journal of molecular histology · 2026Article
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
- YY1/Asprosin/PFKP axis regulates glycolytic metabolic and exacerbates pathological cardiac hypertrophy.Nature communications · 2026Article
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- PDK4-driven lactate accumulation facilitates LPCAT2 lactylation to exacerbate sepsis-induced acute lung injury.Cell death and differentiation · 2026Article
- ZBTB7A-mediated regulation of astrocytic glycolysis in neurodegenerative diseases: insights from literature review and bioinformatics prediction.Frontiers in aging neuroscience · 2026Review
- PDK4 Regulates Inflammatory Injury in Acute-on-chronic Liver Failure by Phosphorylating STAT1-mediated M1 Polarization of Macrophages.Journal of clinical and translational hepatology · 2025Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Identification of immunometabolism-associated genes and immune infiltration in sepsis-induced cardiomyopathy using integrated bioinformatics and machine learning approaches.The Journal of international medical research · 2025Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
Abstract
aimsRecent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. METHODS AND
resultsGene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe-/- mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque.
conclusionsWe have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe-/- mice. These results point toward a promising treatment to combat atherosclerosis.
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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.