Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung 813779, Taiwan.
Institutes of Clinical Medicine, National Yang Ming Chiao Tung University, Hsinchu City 30010, Taiwan.
Int J Mol Sci. 2021 Nov 13;22(22):12277. doi: 10.3390/ijms222212277.
Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium-induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium-induced VSMC calcification process ( < 0.05). The protective effect of DXM in calcified-medium-induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.
血管中层钙化已成为慢性肾脏病（CKD）患者心血管死亡率的一个关键因素。具有成骨转化的血管平滑肌细胞（VSMCs）在血管钙化中起作用。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂可减少活性氧（ROS）的产生和钙化介质诱导的 VSMC 钙化。本研究探讨了 NADPH 氧化酶抑制剂右美沙芬（DXM）对血管钙化的影响。我们使用体外和体内研究来评估 DXM 在高磷血症存在下对动脉变化的影响。在腺嘌呤喂养的 Wistar 大鼠中测试了 DXM 的抗血管钙化作用。高磷培养基诱导 VSMC 产生 ROS 和钙化。DXM 显著减弱了钙化介质诱导的 VSMC 钙化过程中 ROS 产生的增加、ATP 的减少和线粒体膜电位的降低（<0.05）。NADPH 氧化酶抑制剂不能进一步增加 DXM 在钙化介质诱导的 VSMC 钙化中的保护作用，表明 NADPH 氧化酶介导了 DXM 的作用。此外，DXM 降低了 CKD Wistar 大鼠的主动脉钙化。我们的结果表明，DXM 的治疗可以减轻血管氧化应激并改善血管钙化。
