title: Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Myocardial Ischemia/Reperfusion, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Karla
authors.initials: K
authors.lastname: Reichert
authors.affiliation: Laboratory of Myocardial Ischemia/Reperfusion, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Helison Rafael
authors.initials: HR
authors.lastname: Pereira do Carmo
authors.affiliation: Laboratory of Myocardial Ischemia/Reperfusion, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Anali
authors.initials: A
authors.lastname: Galluce Torina
authors.affiliation: Laboratory of Myocardial Ischemia/Reperfusion, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Diógenes de Carvalho
authors.affiliation: Department of Internal Medicine, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Andrei
authors.initials: A
authors.lastname: Carvalho Sposito
authors.affiliation: Department of Surgery, Discipline of Cardiac Surgery, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Karlos Alexandre
authors.initials: KA
authors.lastname: de Souza Vilarinho
authors.affiliation: Department of Surgery, Discipline of Cardiac Surgery, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Lindemberg
authors.initials: L
authors.lastname: da Mota Silveira-Filho
authors.affiliation: Department of Surgery, Discipline of Cardiac Surgery, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
authors.forename: Pedro Paulo
authors.initials: PP
authors.lastname: Martins de Oliveira
authors.affiliation: Laboratory of Myocardial Ischemia/Reperfusion, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.|Department of Surgery, Discipline of Cardiac Surgery, Faculty of Medical Science, State University of Campinas - UNICAMP, Campinas, SP, Brazil.|Section of Pediatric Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Orlando
authors.identifier: http://orcid.org/0000-0002-1455-7155
authors.initials: O
authors.lastname: Petrucci
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D017115:Catheter Ablation; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000924:Anticholesteremic Agents; D007375:Interleukin-1; D052002:NF-kappa B p50 Subunit; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D000069059:Atorvastatin; D020781:Matrix Metalloproteinase 1