ArticleCell death & disease2023
Exploring a new mechanism between lactate and VSMC calcification: PARP1/POLG/UCP2 signaling pathway and imbalance of mitochondrial homeostasis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Lactate-Primed NETosis Modulates Hepatic Regeneration During Acute Liver Failure via the TLR9/KLF15/AJUBA Axis.Cell proliferation · 2026Article
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Plasma metabolites, blood-borne microvesicles, and history of preeclampsia as predictors of coronary artery calcification in postmenopausal women.American journal of physiology. Heart and circulatory physiology · 2026Article
- Identification of mitochondria-related genes in calcific aortic valve disease by integrated analysis of single-cell and bulk transcriptomic atlases.Journal of physiology and biochemistry · 2026Article
- Role of vascular smooth muscle cell pathobiology in sepsis‑induced vasoplegia (Review).International journal of molecular medicine · 2026Review
- Vascular Protection of Poly(ADP-ribose) Polymerase Inhibitors in the Combination Therapy With Vascular Endothelial Growth Factor Signaling Pathway Inhibitors.Reviews in cardiovascular medicine · 2026Review
- UBA52 Overexpression Ameliorates Intracerebral Hemorrhage-Associated Neuronal Apoptosis and Mitochondrial Dysfunction: A Protective Role in Neurons.Molecular neurobiology · 2026Article
- Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.Biological research · 2026Review
- FAM177A1 disrupts SIRT3-SOD2 signaling to drive mitochondrial dysfunction-mediated VSMC phenotypic switching in vascular remodeling.International journal of biological sciences · 2026Article
- DNA Polymerase Gamma Acetylation Governs Mitochondrial Homeostasis and Vascular Cell Senescence.International journal of biological sciences · 2026Article
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- Irisin targets the HK1-glycolysis-NLRP3 pyroptosis axis to prevent chronic kidney disease-associated vascular calcification.Renal failure · 2025Article
- Comprehensive Review of Mechanisms and Translational Perspectives on Programmed Cell Death in Vascular Calcification.Biomolecules · 2025Review
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure.Biomedicines · 2025Review
- Review
- The Roles of Lactate and Lactylation in Diseases Related to Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- A new mechanism of arterial calcification in diabetes: interaction between H3K18 lactylation and CHI3L1.Clinical science (London, England : 1979) · 2025Article
- Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactate leads to the imbalance of mitochondria homeostasis, which then promotes vascular calcification. PARP1 can upregulate osteogenic genes and accelerate vascular calcification. However, the relationship among lactate, PARP1, and mitochondrial homeostasis is unclear. The present study aimed to explore the new molecular mechanism of lactate to promote VSMC calcification by evaluating PARP1 as a breakthrough molecule. A coculture model of VECs and VSMCs was established, and the model revealed that the glycolysis ability and lactate production of VECs were significantly enhanced after incubation in DOM. Osteogenic marker expression, calcium deposition, and apoptosis in VSMCs were decreased after lactate dehydrogenase A knockdown in VECs. Mechanistically, exogenous lactate increased the overall level of PARP and PARylation in VSMCs. PARP1 knockdown inhibited Drp1-mediated mitochondrial fission and partially restored PINK1/Parkin-mediated mitophagy, thereby reducing mitochondrial oxidative stress. Moreover, lactate induced the translocation of PARP1 from the nucleus to the mitochondria, which then combined with POLG and inhibited POLG-mediated mitochondrial DNA synthesis. This process led to the downregulation of mitochondria-encoded genes, disturbance of mitochondrial respiration, and inhibition of oxidative phosphorylation. The knockdown of PARP1 could partially reverse the damage of mitochondrial gene expression and function caused by lactate. Furthermore, UCP2 was upregulated by the PARP1/POLG signal, and UCP2 knockdown inhibited Drp1-mediated mitochondrial fission and partially recovered PINK1/Parkin-mediated mitophagy. Finally, UCP2 knockdown in VSMCs alleviated DOM-caused VSMC calcification in the coculture model. The study results thus suggest that upregulated PARP1 is involved in the mechanism through which lactate accelerates VSMC calcification partly via POLG/UCP2-caused unbalanced mitochondrial homeostasis.
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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.