Atorvastatin dose-dependently reduced collagen synthesis in cardiac fibroblasts stimulated with TGF-beta1 (3.7-fold reduction; 95% CI 1.8-15; P<0.01) or Ang II (5.3-fold reduction; P<0.01).
Does atorvastatin reduce collagen synthesis in cardiac fibroblasts stimulated with TGF-beta1 or AngII?
Atorvastatin directly inhibits collagen production by cardiac fibroblasts in vitro, suggesting an antifibrotic mechanism that may contribute to its antiremodeling effects post-myocardial infarction.
Effect estimate: 3.7-fold reduction (TGF-beta1) / 5.3-fold reduction (Ang II) (95% CI 1.8-15)
p-value: p=< 0.01
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.
Martin et al. (Thu,) conducted a other in Ventricular remodelling after myocardial infarction. Atorvastatin vs. Stimulant alone (TGF-beta1 or Ang II) was evaluated on Collagen synthesis (3.7-fold reduction (TGF-beta1) / 5.3-fold reduction (Ang II), 95% CI 1.8-15, p=< 0.01). Atorvastatin dose-dependently reduced collagen synthesis in cardiac fibroblasts stimulated with TGF-beta1 (3.7-fold reduction; 95% CI 1.8-15; P<0.01) or Ang II (5.3-fold reduction; P<0.01).
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