Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

Autor(es)

Reichert, Karla ; Pereira do Carmo, Helison Rafael ; Torina, Anali Galluce ; de Carvalho, Daniela Diogenes ; Sposito, Andrei Carvalho ; de Souza Vilarinho, Karlos Alexandre ; Silveira-Filho, Lindemberg da Mota ; Martins de Oliveira, Pedro Paulo ; Petrucci, Orlando

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 11, n. 11 NOV 23 2016.
• Citações Web of Science: 16

Resumo

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. (AU)

• Processo FAPESP: 12/09494-3 - Ação da diacereína no remodelamento ventricular esquerdo após infarto agudo do miocárdio: estudo experimental.
• Beneficiário: Karla Reichert
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 11/14550-7 - Ação da diacereina no remodelamento ventricular esquerdo após infarto agudo do miocárdio: estudo experimental
• Beneficiário: Orlando Petrucci Jr
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/09130-1 - Desenvolvimento de solução cardioplégica para transplante cardíaco e proteção miocárdica durante cirurgias cardíacas convencionais
• Beneficiário: Orlando Petrucci Jr
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/10661-4 - Treinamento em preparações de coração isolado tipo working heart e Langendorff clássico
• Beneficiário: Helison Rafael Pereira Do Carmo
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico