ArticleCardiovascular research2016
Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A systematic review on active sites and functions of PIM-1 protein.Human cell · 2022Pooled it
- Yin and Yang of ginsenosides: Molecular mechanisms of bidirectional regulation of angiogenesis.Journal of ginseng research · 2026Review
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- Bacterial vesicles-initiatedTheranostics · 2026Article
- VEGF-B-mediated myofiber types involved in high-fat diet-induced hyperglycemia through PKA-NFATs signaling pathway.Stem cell research & therapy · 2025Article
- Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase.Journal of Zhejiang University. Science. B · 2025Article
- PIM1 instigates endothelial-to-mesenchymal transition to aggravate atherosclerosis.Theranostics · 2025Article
- Role of the portal system in liver regeneration: From molecular mechanisms to clinical management.Liver research (Beijing, China) · 2024Review
- HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.International journal of molecular sciences · 2024Article
- Pim Kinases: Important Regulators of Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Article
- Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition.Molecular medicine reports · 2020Article
- The role of Pim kinase in immunomodulation.American journal of cancer research · 2020Review
- The histone deacetylase inhibitor tubacin mitigates endothelial dysfunction by up-regulating the expression of endothelial nitric oxide synthase.The Journal of biological chemistry · 2019Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018Article
- High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression.Oncotarget · 2017Article
- Redox regulation of gasotransmission in the vascular system: A focus on angiogenesis.Free radical biology & medicine · 2017Review
- The eNOS signalosome and its link to endothelial dysfunction.Pflugers Archiv : European journal of physiology · 2016Review
- MicroRNA-124-3p regulates cell proliferation, invasion, apoptosis, and bioenergetics by targeting PIM1 in astrocytoma.Cancer science · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsPosttranslational modification, such as phosphorylation, plays an essential role in regulating activation of endothelial NO synthase (eNOS). In the present study, we aim to determine whether eNOS could be phosphorylated and regulated by a novel serine/threonine-protein kinase Pim1 in vascular endothelial cells (ECs). METHODS AND
resultsUsing immunoprecipitation and protein kinase assays, we demonstrated that Pim1 specifically interacts with eNOS, which leads to a marked phosphorylation of eNOS at Ser-633 and increased production of nitric oxide (NO). Intriguingly, in response to VEGF stimulation, eNOS phosphorylation at Ser-633 exhibits two distinct phases: transient phosphorylation occurring between 0 and 60 min and sustained phosphorylation occurring between 2 and 24 h, which are mediated by the protein kinase A (PKA) and Pim1, respectively. Inhibiting Pim1 by either pharmacological inhibitor SMI-4a or the dominant-negative form of Pim1 markedly attenuates VEGF-induced tube formation, while Pim1 overexpression significantly increases EC tube formation and migration in an NO-dependent manner. Importantly, Pim1 expression and eNOS phosphorylation at Ser-633 were substantially decreased in high glucose-treated ECs and in the aorta of db/db diabetic mice. Increased Pim1 expression ameliorates impaired vascular angiogenesis in diabetic mice, as determined by an ex vivo aortic ring assay.
conclusionOur findings demonstrate Pim1 as a novel kinase that is responsible for the phosphorylation of eNOS at Ser-633 and enhances EC sprouting of aortic rings from diabetic mice, suggesting that Pim1 could potentially serve as a novel therapeutic target for revascularization strategies.
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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.