1. Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.
- Author
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Reichert K, Pereira do Carmo HR, Galluce Torina A, Diógenes de Carvalho D, Carvalho Sposito A, de Souza Vilarinho KA, da Mota Silveira-Filho L, Martins de Oliveira PP, and Petrucci O
- Subjects
- Animals, Anticholesteremic Agents therapeutic use, Atorvastatin therapeutic use, Catheter Ablation, Disease Models, Animal, Fibrosis, Gene Expression drug effects, Heart Ventricles pathology, Hemodynamics drug effects, Interleukin-1 genetics, Interleukin-1 metabolism, Male, Matrix Metalloproteinase 1 metabolism, Myocardial Infarction drug therapy, Myocardial Infarction pathology, Myocardial Infarction surgery, Myocardium metabolism, Myocardium pathology, NF-kappa B p50 Subunit genetics, NF-kappa B p50 Subunit metabolism, Rats, Rats, Wistar, Tissue Inhibitor of Metalloproteinase-1 metabolism, Anticholesteremic Agents pharmacology, Atorvastatin pharmacology, Collagen metabolism, Ventricular Remodeling drug effects
- Abstract
Purpose: Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI., Methods: Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed., Results: End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50., Conclusion: Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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