Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
The HNPCC Register, Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.
Sci Rep. 2020 Oct 12;10(1):17012. doi: 10.1038/s41598-020-73896-2.
Statins are prescribed to treat hypercholesterolemia and to reduce the risk of cardiovascular disease. However, statin users frequently report myalgia, which can discourage physical activity or cause patients to discontinue statin use, negating the potential benefit of the treatment. Although a proposed mechanism responsible for Statin-Associated Myopathy (SAM) suggests a correlation with impairment of mitochondrial function, the relationship is still poorly understood. Here, we provide evidence that long-term treatment of hypercholesterolemic patients with Simvastatin at a therapeutic dose significantly display increased mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), and platelets compared to untreated controls. Furthermore, the amount of superoxide is higher in mitochondria in PBMCs, and platelets from Simvastatin-treated patients than in untreated controls, and the abundance of mitochondrial superoxide, but not mitochondrial respiration trends with patient-reported myalgia. Ubiquinone (also known as coenzyme Q10) has been suggested as a potential treatment for SAM; however, an 8-week course of oral ubiquinone had no impact on mitochondrial functions or the abundance of superoxide in mitochondria from PBMCs, and platelets. These results demonstrate that long-term treatment with Simvastatin increases respiration and the production of superoxide in mitochondria of PBMCs and platelets.
他汀类药物被开处方用于治疗高胆固醇血症和降低心血管疾病的风险。然而,他汀类药物使用者经常报告肌肉疼痛,这可能会抑制体力活动或导致患者停止使用他汀类药物,从而否定了治疗的潜在益处。虽然一个提出的负责他汀类药物相关肌肉病(SAM)的机制表明与线粒体功能的损伤有关,但这种关系仍不清楚。在这里,我们提供的证据表明,长期用治疗剂量的辛伐他汀治疗高胆固醇血症患者,与未治疗的对照组相比,外周血单核细胞(PBMC)和血小板中的线粒体呼吸明显增加。此外,来自辛伐他汀治疗患者的 PBMC 和血小板中线粒体中的超氧化物含量高于未治疗的对照组,并且线粒体中超氧化物的丰度与患者报告的肌肉疼痛趋势一致,但与线粒体呼吸无关。辅酶 Q10(也称为辅酶 Q10)已被提议作为 SAM 的潜在治疗方法;然而,8 周的口服辅酶 Q10 对 PBMC 和血小板中线粒体功能或超氧化物的丰度没有影响。这些结果表明,长期用辛伐他汀治疗会增加 PBMC 和血小板中线粒体的呼吸和超氧化物的产生。