title: Pleiotropic effects of long-term monotherapy with rosuvastatin in dogs with moderate heart failure.
abstract: OBJECTIVE
  The objective of this study was to investigate the potential pleiotropic effects of rosuvastatin (RSV) in the left ventricular (LV) myocardium of dogs with moderate heart failure (HF).
  
  
  METHODS
  LV tissue was obtained from HF dogs randomized to 3 months therapy with low-dose RSV (n = 7), high-dose RSV (n = 7) or to no therapy (Control, n = 7) and from 7 normal dogs. mRNA and protein expression of prohypertrophic mediator NGFI-A binding protein 1 (Nab1), phosphatase and tensin homolog (PTEN), phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) were measured, as well as that of proinflammatory cytokine interleukin-6 (IL-6), bone marrow-derived stem cell markers cKit and Sca1, vascular endothelial and fibroblast growth factors (VEGF and FGF) and nitric oxide synthase (NOS) isoforms.
  
  
  RESULTS
  Nab1, PTEN, PI3K, mTOR and IL-6 increased in the controls. High-dose RSV reduced expression of Nab1, PTEN, PI3K, mTOR and IL-6 to near-normal levels. cKit and Sca1 significantly increased, while VEGF and FGF decreased in the controls compared to the normal dogs. RSV therapy further increased expression of cKit, Sca1, VEGF and FGF. High-dose RSV normalized the expression of NOS isoforms.
  
  
  CONCLUSIONS
  These pleiotropic effects of RSV may account, in part, for the observed beneficial effect of RSV on LV function and structural remodeling.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zacà
authors.forename: Sudhish
authors.initials: S
authors.lastname: Mishra
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Sharad
authors.initials: S
authors.lastname: Rastogi
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000378:metabolism; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004798:Enzymes; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011506:Proteins; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium