The objective of this study was to investigate potential pleiotropic effects of rosuvastatin (RSV) in left ventricular (LV) myocardium of dogs with moderate heart failure (HF).
LV tissue was obtained from HF dogs randomized to 3 months therapy with low dose (LD) RSV (n=7), high dose (HD) RSV (n=7) or to no therapy (Control, n=7), and from 7 normal (NL) dogs. mRNA and protein expression of pro-hypertrophic mediators NGFI-A binding protein 1 (Nab1), phosphatase and tensin homolog (PTEN), phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR); pro-inflammatory cytokine interleukin-6 (IL-6); bone marrow-derived stem cells (BMSCs) markers cKit and Sca1; vascular endothelial (VEGF) and fibroblast (FGF) growth factors and nitric oxide synthase (NOS) isoforms were measured.
Nab1, PTEN, PI3K, mTOR, and IL-6 increased in Controls. HD 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 Controls compared to NL. RSV therapy further increased expression of cKit, Sca1, VEGF and FGF. HD RSV normalized expression of NOS isoforms.
These pleiotropic effects of RSV may account, in part, for the observed beneficial effect of RSV on LV function and structural remodeling.