Assessing the Effects of Statin-Induced Myopathy on Cardiac and Smooth Muscle Function and the Ability of Vitamin D to Prevent Pathological Changes

Abstract

Evidence suggests low vitamin D levels may be associated with the onset of statin-induced myopathy (SIM), however, physiological and biochemical assessments verifying this are lacking. This study aimed to quantify changes in cardiac, smooth and skeletal muscle integrity in a rodent model of SIM and determine whether vitamin D3 (VitD) treatment could prevent these alterations. 10-12 week-old female Wistar rats were randomly assigned to one of six treatment groups: control, control + VitD (12.5 μg/kg), vehicle-treated control, SIM model (80 mg/kg of simvastatin), SIM + VitD and vehicle-treated SIM. Treatments were administered orally for two weeks after which assessments of cardiac, smooth and skeletal muscle functionality were performed. The onset of SIM significantly impacted upon the mass and functionality of fast twitch-skeletal and cardiac muscle, the latter of which was evident by increased left ventricular mass, hydroxyproline levels (control 2.6 mg/ml; SIM 6.83 mg/ml) and prolonged action potential duration at 90% of repolarisation (control 91.79msec SIM 157.67msec). Statin-induced changes in the myocardium were prevented by the co-administration of VitD (hydroxyproline 4.79 mg/ml; APD90% 90.47msec). Notably the functionality of the vasculature was not significantly impacted by the onset of SIM or co-administration of VitD. Findings from this study suggest the onset of SIM can impact upon myocardial function, whilst the protective effects of statins in the vasculature remain unaffected by the onset of this side effect. Additionally the co-administration of VitD partially prevented these pathological changes, suggesting reduced levels of this lipid soluble hormone may be involved in the onset of SIM.