ArticleProceedings of the National Academy of Sciences of the United States of America2004
Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials.Medicine · 2015 · on this mapPooled it
- Trial
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- Retention of Improved Plantar Sensation in Patients with Type II Diabetes Mellitus and Sensory Peripheral Neuropathy after One Month of Vibrating Insole Therapy: A Pilot Study.Sensors (Basel, Switzerland) · 2024Article
- Liquid plasma promotes angiogenesis through upregulation of endothelial nitric oxide synthase-induced extracellular matrix metabolism: potential applications of liquid plasma for vascular injuries.Cell communication and signaling : CCS · 2024Article
- Shear Stress and RBC-NOS Serine1177 Phosphorylation in Humans: A Dose Response.Life (Basel, Switzerland) · 2021Article
- Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications.Journal of clinical medicine · 2019Review
- Deletion of Robo4 prevents high-fat diet-induced adipose artery and systemic metabolic dysfunction.Microcirculation (New York, N.Y. : 1994) · 2019Article
- cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway.Basic research in cardiology · 2018Review
- Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Hematopoietic stem cell transplant-associated thrombotic microangiopathy: current paradigm and novel therapies.Bone marrow transplantation · 2018Review
- Fluvastatin attenuated the effect of expression of β1 integrin in PAN-treated podocytes by inhibiting reactive oxygen species.Molecular and cellular biochemistry · 2015Article
- Pleiotropic effects of pitavastatin.British journal of clinical pharmacology · 2012Review
- Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells.Respiratory research · 2011Article
- Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells.British journal of pharmacology · 2011Article
- NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models.British journal of pharmacology · 2009Article
- Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics.Pharmacology & therapeutics · 2009Review
- Nitric oxide in transplantation-related thrombotic microangiopathy.Bone marrow transplantation · 2009Article
- Inhibitory effects of NO-fluvastatin on proliferation of human lens epithelial cells in vitro by modulating cell cycle regulatory proteins.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2008Article
- Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective.Antioxidants & redox signaling · 2008Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. Their pharmacological activity on atherosclerotic plaque stability and vascular inflammation appears to be mediated, at least in part, by nitric oxide (NO). With the aim of enhancing the nonlipid-lowering properties of selected statins, we introduced a NO-releasing moiety into the structure of pravastatin (NCX 6550) and fluvastatin (NCX 6553). NO release was evaluated as nitrosylhemoglobin adduct formation by using EPR spectroscopy in rat blood. Both compounds produced a linear time-dependent increase in nitrosylhemoglobin formation, which is consistent with slow NO release kinetics. In PC12 cells, unlike their native statins, both compounds stimulated cGMP formation (NCX 6550, EC(50) = 2.3 +/- 0.2 microM; NCX 6553, EC(50) = 2.7 +/- 0.2 microM). Moreover, NCX 6550 potently inhibited cell proliferation in rat aortic smooth muscle cells (IC(50) = 2.2 +/- 0.3 microM) with a mechanism that involved both the polyamine and HMG-CoA reductase signaling pathways. Hence, mevalonate or putrescine partially reverted the effects of NCX 6550 and their combination was fully effective. In RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (1 microg/ml), NCX 6550, but not pravastatin, significantly decreased inducible NO synthase and cyclooxygenase-2 protein expression as well as nitrite accumulation. All together, the data show that the previously undescribed NO-releasing statins retain HMG-CoA reductase inhibitory activity and release bioactive NO slowly. Among the additional properties, compared with native statins, the NO-releasing statins show enhanced antiinflammatory effects. Thus, NO-releasing statins represent an interesting class of drugs having potential in the therapy of disorders associated with endothelial dysfunction and vascular inflammation.
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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.