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IN VITRO INHIBITORY EFFECTS OF ATORVASTATIN ON CARDIAC FIBROBLASTS: IMPLICATIONS FOR VENTRICULAR REMODELLING
Author(s) -
Martin Jennifer,
Denver Rachel,
Bailey Michael,
Krum Henry
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2005.04256.x
Subject(s) - atorvastatin , cardiac fibrosis , endocrinology , extracellular matrix , medicine , fibroblast , fibrosis , angiotensin ii , ventricular remodeling , statin , chemistry , pharmacology , myocardial infarction , in vitro , biochemistry , receptor
SUMMARY 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)‐β1 (TGF‐β1) 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‐β1 and AngII‐induced increases in α(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.