Statins are effective drugs in reducing cardiovascular morbidity and mortality by inhibiting cholesterol synthesis. These effects are primarily beneficial for the patient’s vascular system. A significant number of statin users suffer from muscle complaints probably due to mitochondrial dysfunction, a mechanism that has recently been elucidated. This has raised our interest in exploring the effects of statins on cardiac muscle cells in an era where the elderly and patients with poorer functioning hearts and less metabolic spare capacity start dominating our patient population. Here, we investigated the effects of statins on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-derived CMs). hiPSC-derived CMs were exposed to simvastatin, atorvastatin, rosuvastatin, and cerivastatin at increasing concentrations. Metabolic assays and fluorescent microscopy were employed to evaluate cellular viability, metabolic capacity, respiration, intracellular acidity, and mitochondrial membrane potential and morphology. Over a concentration range of 0.3–100 µM, simvastatin lactone and atorvastatin acid showed a significant reduction in cellular viability by 42–64%. Simvastatin lactone was the most potent inhibitor of basal and maximal respiration by 56% and 73%, respectively, whereas simvastatin acid and cerivastatin acid only reduced maximal respiration by 50% and 42%, respectively. Simvastatin acid and lactone and atorvastatin acid significantly decreased mitochondrial membrane potential by 20%, 6% and 3%, respectively. The more hydrophilic atorvastatin acid did not seem to affect cardiomyocyte metabolism. This calls for further research on the translatability to the clinical setting, in which a more conscientious approach to statin prescribing might be considered, especially regarding the current shift in population toward older patients with poor cardiac function.

他汀类药物是通过抑制胆固醇合成来降低心血管发病率和死亡率的有效药物。这些作用主要对患者的血管系统有益。大量他汀类药物使用者可能因线粒体功能障碍而遭受肌肉不适，这一机制最近已被阐明。这引起了我们对探索他汀类药物对心肌细胞的影响的兴趣，因为在这个时代，老年人和心脏功能较差且代谢备用能力较低的患者开始主导我们的患者群体。在这里，我们研究了他汀类药物对人诱导多能干细胞衍生的心肌细胞（hiPSC 衍生的 CM）的影响。 hiPSC 衍生的 CM 暴露于浓度逐渐增加的辛伐他汀、阿托伐他汀、瑞舒伐他汀和西立伐他汀。采用代谢测定和荧光显微镜来评估细胞活力、代谢能力、呼吸、细胞内酸度以及线粒体膜电位和形态。在 0.3–100 µM 浓度范围内，辛伐他汀内酯和阿托伐他汀酸显示细胞活力显着降低 42–64%。辛伐他汀内酯是最有效的基础呼吸和最大呼吸抑制剂，分别降低 56% 和 73%，而辛伐他汀酸和西立伐他汀酸仅分别降低最大呼吸 50% 和 42%。辛伐他汀酸、内酯和阿托伐他汀酸分别显着降低线粒体膜电位20%、6%和3%。更亲水的阿托伐他汀酸似乎不影响心肌细胞代谢。这需要进一步研究临床环境的可转化性，其中可能考虑采取更认真的他汀类药物处方方法，特别是考虑到当前人口转向心功能较差的老年患者。