ArticleScientific reports2015
Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Integrative transcriptomics and human tibial artery validation identifyJVS-vascular science · 2026Article
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- Single cell and spatial transcriptomic profiling of the type 2 diabetic coronary microcirculation and myocardium.Basic research in cardiology · 2025Article
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms.Clinical epigenetics · 2025Review
- Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure.Biomedicines · 2025Review
- Therapeutic Targeting of Decr1 Ameliorates Cardiomyopathy by Suppressing Mitochondrial Fatty Acid Oxidation in Diabetic Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease.Journal of nephrology · 2025Review
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
- Multiomics identification of ALDH9A1 as a crucial immunoregulatory molecule involved in calcific aortic valve disease.Scientific reports · 2024Article
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- The Role of Mitochondrial Dysfunction in CKD-Related Vascular Calcification: From Mechanisms to Therapeutics.Kidney international reports · 2024Review
- Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS.Cellular and molecular life sciences : CMLS · 2024Article
- Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice.Diabetes & metabolism journal · 2024Article
- Biomarkers of Metabolic Adaptation to High Dietary Fats in a Mouse Model of Obesity Resistance.Metabolites · 2024Article
- Article
- Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification.International journal of molecular sciences · 2023Article
- Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.Cardiovascular research · 2023Article
- The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.Diabetes & metabolism journal · 2023Review
Corrections and comments
- Erratum issuedCorrigendum: Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation.2016 · Ha, Chae-Myung [corrected to Ha, Chae-Myeong]
Authors and funding
21 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification, a pathologic response to defective calcium and phosphate homeostasis, is strongly associated with cardiovascular mortality and morbidity. In this study, we have observed that pyruvate dehydrogenase kinase 4 (PDK4) is upregulated and pyruvate dehydrogenase complex phosphorylation is increased in calcifying vascular smooth muscle cells (VSMCs) and in calcified vessels of patients with atherosclerosis, suggesting that PDK4 plays an important role in vascular calcification. Both genetic and pharmacological inhibition of PDK4 ameliorated the calcification in phosphate-treated VSMCs and aortic rings and in vitamin D3-treated mice. PDK4 augmented the osteogenic differentiation of VSMCs by phosphorylating SMAD1/5/8 via direct interaction, which enhances BMP2 signaling. Furthermore, increased expression of PDK4 in phosphate-treated VSMCs induced mitochondrial dysfunction followed by apoptosis. Taken together, our results show that upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification.
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