Prolonged exposure to simvastatin affects coenzyme Q9/10 status leading to impaired mitochondrial respiratory capacity and reduced viability of cultured cardiac cells

This study investigates the effects of prolonged simvastatin exposure on coenzyme Q9/10 (CoQ9/10) levels, an essential component of antioxidant defense, in cultured cardiac cells. Statins, commonly used to manage dyslipidemia and reduce cardiovascular risk, may impair mitochondrial function, but their impact on CoQ10 depletion and oxidative stress is not well understood. We examined the influence of simvastatin on mitochondrial oxidative capacity, reactive oxygen species (ROS) production, and CoQ9/10 status at concentrations of 0.3, 0.6, 1.25, 2.5, 5, 10, and 20 μM, over durations of 24, 48, and 72 h. Using an in vitro model of cultured H9c2 cardiomyoblasts, our results showed that short-term exposure (24 h) at lower concentrations (<5 μM) enhanced cytosolic and mitochondrial ROS levels without affecting mitochondrial function or CoQ9/10 status. However, prolonged exposure to higher concentrations (≥10 μM for >48 h) resulted in impaired mitochondrial oxidative capacity, indicated by increased proton leak and elevated ROS levels, which were followed by significantly reduced cell viability. These findings suggest that prolonged, high-dose simvastatin exposure may disrupt the oxidative balance of CoQ9/10, leading to myocardial injury. This research addresses a gap in understanding the long-term effects of statins on mitochondrial health and underscores the need for further studies to optimize statin therapy and minimize adverse effects on myocardial function.