ArticleCardiovascular research2021
Adenosine kinase is critical for neointima formation after vascular injury by inducing aberrant DNA hypermethylation.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Class Effect of SGLT2 Inhibitors Against Doxorubicin-Induced Cardiotoxicity via Regulating Adenosine Kinase Mediated-Cardiac Oxidative Stress.Cardiovascular drugs and therapy · 2026Article
- Neointimal hyperplasia and vascular restenosis: from molecular mechanisms to therapeutic interventions.Molecular biomedicine · 2026Review
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development.International journal of molecular sciences · 2025Article
- Non-Canonical Functions of Adenosine Receptors: Emerging Roles in Metabolism, Immunometabolism, and Epigenetic Regulation.International journal of molecular sciences · 2025Review
- The functional significance of vascular DNA hypermethylation in atherosclerosis: a historical perspective.Frontiers in pharmacology · 2025Review
- Identification of Potential Diagnostic Biomarkers and Drug Targets for Endometriosis from a Genetic Perspective: A Mendelian Randomization Study.Gynecologic and obstetric investigation · 2025Article
- Adenosine kinase inhibition protects mice from abdominal aortic aneurysm via epigenetic modulation of VSMC inflammation.Cardiovascular research · 2024Article
- RNA sequencing and proteomic profiling reveal alterations by MPTP in chronic stomach mucosal injury in tree shrew Chinese (Tupaia belangeri chinensis).Scientific reports · 2024Article
- Developmental and foliation changes due to dysregulation of adenosine kinase in the cerebellum.Scientific reports · 2023Article
- Methyltransferase-like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation.Cell proliferation · 2023Article
- Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation.Journal of nanobiotechnology · 2023Article
- Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway.Drug design, development and therapy · 2023Article
- Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype.Journal of molecular and cellular cardiology · 2023Article
- Epigenetic modifications as therapeutic targets in atherosclerosis: a focus on DNA methylation and non-coding RNAs.Frontiers in cardiovascular medicine · 2023Review
- DR1 Activation Inhibits the Proliferation of Vascular Smooth Muscle Cells through Increasing Endogenous HAging and disease · 2022Article
- Adenosine-Metabolizing Enzymes, Adenosine Kinase and Adenosine Deaminase, in Cancer.Biomolecules · 2022Review
- Association of the DNA Methyltransferase and Folate Cycle Enzymes' Gene Polymorphisms with Coronary Restenosis.Life (Basel, Switzerland) · 2022Article
- Adenosine kinase: An epigenetic modulator in development and disease.Neurochemistry international · 2021Review
- Adenosine kinase: A key regulator of purinergic physiology.Biochemical pharmacology · 2021Review
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsAdenosine receptors and extracellular adenosine have been demonstrated to modulate vascular smooth muscle cell (VSMC) proliferation and neointima formation. Adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels but is function in VSMC remains unclear. Here, we investigated the role of ADK in vascular injury-induced smooth muscle proliferation and delineated the mechanisms underlying its action. METHODS AND
resultsWe found that ADK expression was higher in the neointima of injured vessels and in platelet-derived growth factor-treated VSMCs. Genetic and pharmacological inhibition of ADK was enough to attenuate arterial injury-induced neointima formation due to inhibition of VSMC proliferation. Mechanistically, using infinium methylation assays and bisulfite sequencing, we showed that ADK metabolized the intracellular adenosine and potentiated the transmethylation pathway, then induced the aberrant DNA hypermethylation. Pharmacological inhibition of aberrant DNA hypermethylation increased KLF4 expression and suppressed VSMC proliferation as well as the neointima formation. Importantly, in human femoral arteries, we observed increased ADK expression and DNA hypermethylation as well as decreased KLF4 expression in neointimal VSMCs of stenotic vessels suggesting that our findings in mice are relevant for human disease and may hold translational significance.
conclusionOur study unravels a novel mechanism by which ADK promotes VSMC proliferation via inducing aberrant DNA hypermethylation, thereby down-regulating KLF4 expression and promoting neointima formation. These findings advance the possibility of targeting ADK as an epigenetic modulator to combat vascular injury.
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