ArticleLife sciences2008
Disparate effects of simvastatin on angiogenesis during hypoxia and inflammation.
Article in Life sciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Cellular mechanisms involved in the pathogenesis of airway remodeling in chronic lung disease.European clinical respiratory journal · 2022Article
- Remodeling tumor microenvironment by liposomal codelivery of DMXAA and simvastatin inhibits malignant melanoma progression.Scientific reports · 2021Article
- Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High-Fat Diet: Role of Angiogenesis.Oxidative medicine and cellular longevity · 2021Article
- A Boolean Model of Microvascular Rarefaction to Predict Treatment Outcomes in Renal Disease.Scientific reports · 2020Article
- Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia.Biology of sex differences · 2019Article
- Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris.British journal of pharmacology · 2019Article
- Simvastatin reduces the carcinogenic effect of 3-methylcholanthrene in renal epithelial cells through histone deacetylase 1 inhibition and RhoA reactivation.Scientific reports · 2019Article
- Activation of AMPK by simvastatin inhibited breast tumor angiogenesis via impeding HIF-1α-induced pro-angiogenic factor.Cancer science · 2018Article
- Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment.Acta biomaterialia · 2018Article
- Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model.Plastic and reconstructive surgery. Global open · 2017Article
- Topical simvastatin promotes healing of Staphylococcus aureus-contaminated cutaneous wounds.International wound journal · 2016Article
- Early atherosclerosis aggravates renal microvascular loss and fibrosis in swine renal artery stenosis.Journal of the American Society of Hypertension : JASH · 2016Article
- Gained in translation: protective paradigms for the poststenotic kidney.Hypertension (Dallas, Tex. : 1979) · 2015Review
- Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.Stem cell research & therapy · 2015Article
- The many roles of statins in ischemic stroke.Current neuropharmacology · 2014Article
- Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2013Article
- Review
- Therapeutic angiogenesis in critical limb ischemia.Angiology · 2013Review
- The effect of atorvastatin on survival of rat ischemic flap.The Kaohsiung journal of medical sciences · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsStudies have shown that some of statin's pleiotropic effects were achieved by either promotion or inhibition of angiogenesis, depending on the underlying disease. This study tested the hypothesis that the angiogenic potential of simvastatin is related to the microenvironmental conditions. MAIN
methodsHuman umbilical vein endothelial cells (HUVEC) were studied after exposure to hypoxia or the inflammatory factors tumor necrosis factor (TNF)-alpha, with or without co-incubation with simvastatin (1 micromol/L) and mevalonate. HUVEC angiogenesis was evaluated by tube formation, migration, and proliferation assays. Hypoxia inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), Akt, endothelium nitric oxide synthase (e-NOS), and oxidative stress were evaluated. KEY
findingsHUVEC angiogenesis increased during hypoxia (tube length 14.7+/-0.5 vs. 7.8+/-0.6 mm, p<0.05) and further enhanced by simvastatin (19.3+/-1.1 mm, p<0.05 vs. hypoxia alone), which downregulated the expression of the HIF-1 inhibitor PHD2 and upregulated HIF-1alpha, VEGF, and Akt, without changing oxidative stress or eNOS. Incubation with TNF-alpha promoted HUVEC angiogenesis (7.4+/-0.2 vs. 6.5+/-0.2 mm, p<0.05) with increased oxidative stress. However, simvastatin inhibited this promotion (2.5+/-0.3 mm, p<0.001 vs. TNF-alpha alone) by decreasing oxidative stress, VEGF, Akt, and eNOS. SIGNIFICANCE: We conclude that at the same dosage, simvastatin can either promote or inhibit angiogenesis, possibly by activating upstream regulators of HIF-1alpha in hypoxia, but conversely interfering with angiogenic signaling downstream to inflammation. These opposing angiogenic effects should be considered in the therapeutic strategies with statins.
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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.