ArticleThe Journal of biological chemistry2011
The multifunctional Ca2+/calmodulin-dependent kinase II delta (CaMKIIdelta) controls neointima formation after carotid ligation and vascular smooth muscle cell proliferation through cell cycle regulation by p21.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 60 citations in OpenAlex.
- EHMT2 aggravates vascular remodeling via epigenetic inhibition of GADD45G.Experimental & molecular medicine · 2026Article
- Profiling of RBM20-Regulated CaMKIIδ Splice Variants Across the Heart, Skeletal Muscle, and Olfactory Bulbs.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Inositol 1,4,5-Trisphosphate Receptors Regulate Vascular Smooth Muscle Cell Proliferation and Neointima Formation in Mice.Journal of the American Heart Association · 2024Article
- Role of CaMKII in diabetes induced vascular injury and its interaction with anti-diabetes therapy.Reviews in endocrine & metabolic disorders · 2024Review
- Regulation of Smooth Muscle Cell Proliferation by Mitochondrial Ca2+ in Type 2 Diabetes.International journal of molecular sciences · 2023Article
- The mitochondrial regulation of smooth muscle cell proliferation in type 2 diabetes.bioRxiv : the preprint server for biology · 2023Article
- CaMKII as a Therapeutic Target in Cardiovascular Disease.Annual review of pharmacology and toxicology · 2023Review
- CaMKII Splice Variants in Vascular Smooth Muscle Cells: The Next Step or Redundancy?International journal of molecular sciences · 2022Review
- Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling.JCI insight · 2021Article
- Quantifying endothelial cell proliferation in the zebrafish embryo.F1000Research · 2021Article
- Redox and Inflammatory Signaling, the Unfolded Protein Response, and the Pathogenesis of Pulmonary Hypertension.Advances in experimental medicine and biology · 2021Article
- Smooth muscle cell-specific fibronectin-EDA mediates phenotypic switching and neointimal hyperplasia.The Journal of clinical investigation · 2020Article
- Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.Journal of vascular research · 2020Article
- Thymine DNA glycosylase is a key regulator of CaMKIIγ expression and vascular smooth muscle phenotype.American journal of physiology. Heart and circulatory physiology · 2019Article
- Effects of icariin on long noncoding RNA and mRNA expression profile in the aortas of apoE-deficient mice.Bioscience reports · 2019Article
- Metabolic Stress.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Considering the Role of Murine Double Minute 2 in the Cardiovascular System?Frontiers in cell and developmental biology · 2019Review
- Calcium/calmodulin-dependent kinase 2 mediates Epac-induced spontaneous transient outward currents in rat vascular smooth muscle.The Journal of physiology · 2017Article
- Redox regulation of the actin cytoskeleton and its role in the vascular system.Free radical biology & medicine · 2017Review
- Oxidized CaMKII promotes asthma through the activation of mast cells.JCI insight · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) promotes vascular smooth muscle (VSMC) proliferation. However, the signaling pathways mediating CAMKII-dependent proliferative effects in vivo are poorly understood. This study tested the hypothesis that CaMKIIδ mediates neointimal proliferation after carotid artery ligation by regulating expression and activity of cell cycle regulators, particularly at the G1/S checkpoint. Data herein indicate that 14 days after carotid ligation, C57Bl/6 mice developed a marked neointima with robust CaMKII protein expression. In particular, only the CaMKII isoform δ was increased as demonstrated by quantitative RT-PCR. Genetic deletion of CaMKII δ prevented injury-induced neointimal hyperplasia and cell proliferation in the intima and media. In ligated carotids of control mice, the proliferative cell cycle markers cdk2, cyclin E, and cyclin D1 were activated. In contrast, in CaMKIIδ(-/-) mice, we detected a reduction in proliferative cell cycle regulators as well as an increase in the cell cycle inhibitor p21. This expression profile was confirmed in cultured CaMKIIδ(-/-) VSMC, in which cdk2 and cdk4 activity was decreased. Toward understanding how CAMKIIδ affects p53, a transcriptional regulator of p21, we examined p53 pathway components. Our data indicate that p53 is elevated in CAMKIIδ(-/-) VSMC, whereas phosphorylation of the p53-specific E3 ligase, Mdm2, was decreased. In conclusion, CaMKII stimulates neointima proliferation after vascular injury by regulating cell proliferation through inhibition of p21 and induction of Mdm-2-mediated degradation of p53.
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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.