title: In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodelling.
abstract: 1. Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2. Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3. The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-beta1 (TGF-beta1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8-15; P < 0.01) and 5.3-fold reduction (95% CI 1.8-7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-beta1 and AngII-induced increases in alpha(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4. Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins.
authors.affiliation: National Health and Medical Research Council of Australia Centre for Clincial Research and Excellence in Therapeutics, Epidemiology and Preventive Medicine, Monash University/Alfred Hospital, Melbourne, Victoria, Australia. jhmartin@medstv.unimelb.edu.au
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martin
authors.forename: Rachel
authors.initials: R
authors.lastname: Denver
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D011347:Procollagen / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling
chemical_list: C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011347:Procollagen; D011758:Pyrroles; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003094:Collagen; D000069059:Atorvastatin