ArticleThe Journal of clinical investigation2001
Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 3 of them syntheses that pooled it.
What it found
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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
122 citing papers in PubMed, 3 syntheses or guidelines pooled it, 484 citations in OpenAlex.
- Effects of statin treatment on cardiac function in patients with chronic heart failure: a meta-analysis of randomized controlled trials.Clinical cardiology · 2011Pooled it
- Statins as antiarrhythmics: a systematic review part I: effects on risk of atrial fibrillation.Clinical cardiology · 2009Pooled it
- Statins in the treatment of chronic heart failure: a systematic review.PLoS medicine · 2006Pooled it
- Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation.Arteriosclerosis, thrombosis, and vascular biology · 2013Trial
- Simvastatin as a treatment for pulmonary hypertension trial.American journal of respiratory and critical care medicine · 2010 · on this mapTrial
- Effects of combined therapy of Xuezhikang Capsule and Valsartan on hypertensive left ventricular hypertrophy and heart rate turbulence.Chinese journal of integrative medicine · 2010Trial
- Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure.Heart (British Cardiac Society) · 2005Trial
- Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy.Circulation · 2003Trial
- Statin-Induced Coenzyme Q Deficiency Induces Metabolic Reprogramming in Astrocytes.Antioxidants (Basel, Switzerland) · 2026Article
- KCNA2 variants cause dilated cardiomyopathy, obesity and sleep apnea through RAC-ERK pathway.EMBO molecular medicine · 2026Article
- Cardiomyocyte Rac1 signaling in hypertrophy, arrhythmia, and cardiac stress adaptation.Journal of molecular and cellular cardiology plus · 2025Review
- Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.Journal of the American Heart Association · 2024Article
- RhoA/ROCK Pathway Is Upregulated in Experimental Autoimmune Myocarditis and Is Inhibited by Simvastatin at the Stage of Myosin Light Chain Phosphorylation.Biomedicines · 2024Article
- Potential Benefits and Risks Associated with the Use of Statins.Pharmaceutics · 2024 · on this mapReview
- Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice.Cardiovascular toxicology · 2024Article
- Understanding the molecular mechanisms of statin pleiotropic effects.Archives of toxicology · 2023Review
- Cannabinoid receptor agonist attenuates angiotensin II-induced enlargement and mitochondrial dysfunction in rat atrial cardiomyocytes.Frontiers in pharmacology · 2023Article
- Statins Protect Against Early Stages of Doxorubicin-induced Cardiotoxicity Through the Regulation of Akt Signaling and SERCA2.CJC open · 2022Article
- NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction.Antioxidants (Basel, Switzerland) · 2022Review
- Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. The hypertrophic process is mediated, in part, by small G proteins of the Rho family. We hypothesized that statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, inhibit cardiac hypertrophy by blocking Rho isoprenylation. We treated neonatal rat cardiac myocytes with angiotensin II (AngII) with and without simvastatin (Sim) and found that Sim decreased AngII-induced protein content, [3H] leucine uptake, and atrial natriuretic factor (ANF) promoter activity. These effects were associated with decreases in cell size, membrane Rho activity, superoxide anion (O2*-) production, and intracellular oxidation, and were reversed with L-mevalonate or geranylgeranylpyrophosphate, but not with farnesylpyrophosphate or cholesterol. Treatments with the Rho inhibitor C3 exotoxin and with cell-permeable superoxide dismutase also decreased AngII-induced O2*- production and myocyte hypertrophy. Overexpression of the dominant-negative Rho mutant N17Rac1 completely inhibited AngII-induced intracellular oxidation and ANF promoter activity, while N19RhoA partially inhibited it, and N17Cdc42 had no effect. Indeed, Sim inhibited cardiac hypertrophy and decreased myocardial Rac1 activity and O2*- production in rats treated with AngII infusion or subjected to transaortic constriction. These findings suggest that statins prevent the development of cardiac hypertrophy through an antioxidant mechanism involving inhibition of Rac1.
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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.