ArticleCell death & disease2020
PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 93 citations in OpenAlex.
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- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- Calcium and TRPML-Mediated Autophagy: Implications in Cancer, Cardiovascular Diseases, and Cardio-Oncology.Cardiovascular toxicology · 2026Review
- Exercise Metabolic Memory Halts Pathological Cardiac Hypertrophy via PDK4.Circulation research · 2026Article
- mScientific reports · 2026Article
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
- Time-course ATAC-seq and RNA-seq analysis of porcine synovium-derived mesenchymal stem cells under in vitro osteogenic induction.Epigenetics & chromatin · 2026Article
- Mitochondrial interplay with membrane organelles in health and disease.Cell communication and signaling : CCS · 2026Review
- Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
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- The Pathophysiological Role of Mitochondria-associated Membranes in Coronary Artery Disease and Atherosclerosis.Current medicinal chemistry · 2026Review
- Integrative transcriptomics and human tibial artery validation identifyJVS-vascular science · 2026Article
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- Irisin targets the HK1-glycolysis-NLRP3 pyroptosis axis to prevent chronic kidney disease-associated vascular calcification.Renal failure · 2025Article
- Single cell and spatial transcriptomic profiling of the type 2 diabetic coronary microcirculation and myocardium.Basic research in cardiology · 2025Article
- Single-Cell Transcriptomics of Human Acute Myocardial Infarction Reveals Oxidative Stress-Associated Cardiomyocyte Subpopulations and Candidate Predictive Signatures.Antioxidants (Basel, Switzerland) · 2025Article
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- SIRT1/PGC-1α/Mfn2 pathway regulates mitochondrial homeostasis in VSMC to attenuate aging-related vascular calcification.Scientific reports · 2025Article
- Review
- Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy regulation. Previous studies suggested that PDK4 is increased in the calcified vessels of patients with atherosclerosis and is closely associated with mitochondrial function, but the precise regulatory mechanisms remain largely unknown. This study aims to investigate the role of PDK4 in vascular calcification and the molecular mechanisms involved. Using a variety of complementary techniques, we found impaired autophagic activity in the process of vascular smooth muscle cells (VSMCs) calcification, whereas knocking down PDK4 had the opposite effect. PDK4 drives the metabolic reprogramming of VSMCs towards a Warburg effect, and the inhibition of PDK4 abrogates VSMCs calcification. Mechanistically, PDK4 disturbs the integrity of the mitochondria-associated endoplasmic reticulum membrane, concomitantly impairing mitochondrial respiratory capacity, which contributes to a decrease in lysosomal degradation by inhibiting the V-ATPase and lactate dehydrogenase B interaction. PDK4 also inhibits the nuclear translocation of the transcription factor EB, thus inhibiting lysosomal function. These changes result in the interruption of autophagic flux, which accelerates calcium deposition in VSMCs. In addition, glycolysis serves as a metabolic adaptation to improve VSMCs oxidative stress resistance, whereas inhibition of glycolysis by 2-deoxy-D-glucose induces the apoptosis of VSMCs and increases the calcium deposition in VSMCs. Our results suggest that PDK4 plays a key role in vascular calcification through autophagy inhibition and metabolic reprogramming.
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