Simvastatin prevents decreased SERCA2a activity in non-ischemic heart failure in rabbits via inhibition of β-adrenergic signaling

Long-term activation of β-adrenergic signaling with alterations in calcium regulatory proteins is critical for cardiac dysfunction in chronic heart failure (CHF), and statins have been shown to have beneficial effects leading to the improvement of heart failure (HF). In this study, rabbits with HF treated with simvastatin exhibited an increased ejection fraction and left ventricular β1-adrenergic receptor density and cAMP levels, in addition to a decreased heart rate and plasma levels of brain natriuretic peptide and norepinephrine, compared to animals with HF induced by combined aortic insufficiency and aortic constriction. Moreover, the expression and activity of SERCA2a and PKA and the ratio of ser16-phosphorated PLB to total PLB were higher in rabbits with HF treated with simvastatin, whereas protein phosphatase 1 alpha expression was reduced compared to untreated animals with HF. These data suggest that simvastatin prevents decreased SERCA2a activity via the inhibition of β-adrenergic signaling in non-ischemic heart failure in rabbits.