Evidence map›Paper›PMID 20525309›Full record

ArticleJournal of biomedical science2010

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation.

Ye-Ming Lee, Wei-Fan Chen, Duen-Suey Chou, Thanasekaran Jayakumar, Ssu-Yu Hou, Jie-Jen Lee, George Hsiao, Joen-Rong Sheu

Open access · diamondAbstract read
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In one paragraph

Article in Journal of biomedical science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

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  8. The vasculature in chagas disease.Advances in parasitology · 2011
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Ye-Ming LeeDepartment of Pharmacology, Taipei Medical University, Taipei, Taiwan. sheujr@tmu.edu.tw
Wei-Fan Chen
Duen-Suey Chou
Thanasekaran Jayakumar
Ssu-Yu Hou
Jie-Jen Lee
George Hsiao
Joen-Rong Sheu
Taipei Medical University · TWMackay Memorial Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin) may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved.

methodsThe aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin.

resultsSimvastatin (20-50 microM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin). Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2) formation, and phospholipase C (PLC)gamma2, protein kinase C (PKC), and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs) phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and endothelial nitric oxide synthase (eNOS) expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCgamma2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation.

conclusionThe most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP-eNOS/NO-cyclic GMP pathway, resulting in inhibition of the PLCgamma2-PKC-p38 MAPK-TxA2 cascade, and finally inhibition of platelet aggregation.

Indexed as

Calcium SignalingCell Adhesion MoleculesCollagenCyclic AMPCyclic GMPHumansHydroxyl RadicalHydroxymethylglutaryl-CoA Reductase InhibitorsIn Vitro TechniquesMAP Kinase Signaling SystemMicrofilament ProteinsMitogen-Activated Protein Kinase KinasesNitric OxideNitric Oxide Synthase Type IIINucleotides, CyclicPhospholipase C gammaCell Adhesion MoleculesCollagenCyclic AMPCyclic GMPHydroxyl RadicalHydroxymethylglutaryl-CoA Reductase InhibitorsMicrofilament ProteinsMitogen-Activated Protein Kinase KinasesNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanNucleotides, CyclicPhospholipase C gammaPhosphoproteinsPlatelet Aggregation InhibitorsProtein Kinase CSimvastatinThromboxane A2Vasodilator-Stimulated Phosphoprotein

Identifiers

PMID20525309
PMCPMC2894762
OpenAlexW2098266773

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LicenceCC BY
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Registered trials

None linked

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.