Background: The pathological role of cytochrome c oxidase 5A (COX5A) in vascular neointima formation remains unknown. Aim: This study aims to investigate the role of COX5A on platelet-derived growth factor BB (PDGFBB)- mediated smooth muscle phenotypic modulation and neointima formation and clarify the molecular mechanisms behind this effect. Methods: For in vitro assays, human aortic vascular smooth muscle cells (HA-VSMCs) were transfected with pcDNA3.1-COX5A and COX5A siRNA to overexpress and knockdown COX5A, respectively. Mitochondrial complex IV activity, oxygen consumption rate (OCR), H2O2 and ATP production, reactive oxygen species (ROS) generation, cell proliferation, and migration were measured. For in vivo assays, rats after balloon injury (BI) were injected with recombinant lentivirus carrying the COX5A gene. Mitochondrial COX5A expression, carotid arterial morphology, mitochondrial ultrastructure, and ROS were measured. Results: The results showed that PDGF-BB reduced the level and altered the distribution of COX5A in mitochondria, as well as reduced complex IV activity, ATP synthesis, and OCR while increasing H2O2 synthesis, ROS production, and cell proliferation and migration. These effects were reversed by overexpression of COX5A and aggravated by COX5A knockdown. In addition, COX5A overexpression attenuated BI-induced neointima formation, muscle fiber area ratio, VSMC migration to the intima, mitochondrial ultrastructural damage, and vascular ROS generation. Conclusion: The present study demonstrated that COX5A protects VSMCs against phenotypic modulation by improving mitochondrial respiratory function and attenuating mitochondrial damage, as well as reducing oxidative stress, thereby preventing neointima formation.

中文翻译：

---

细胞色素 C 氧化酶 5A (COX5A) 对线粒体紊乱和氧化应激在 VSMC 表型调节和新内膜形成中的保护作用

背景：细胞色素 c 氧化酶 5A (COX5A) 在血管新内膜形成中的病理作用仍不清楚。目的：本研究旨在探讨 COX5A 对血小板衍生生长因子 BB (PDGFBB) 介导的平滑肌表型调节和新内膜形成的作用，并阐明这种作用背后的分子机制。方法：在体外测定中，用 pcDNA3.1-COX5A 和 COX5A siRNA 转染人主动脉血管平滑肌细胞 (HA-VSMC)，分别过表达和敲低 COX5A。测量线粒体复合物 IV 活性、耗氧率 (OCR)、H2O2 和 ATP 产生、活性氧 (ROS) 产生、细胞增殖和迁移。对于体内测定，球囊损伤（BI）后的大鼠被注射携带COX5A基因的重组慢病毒。测量线粒体 COX5A 表达、颈动脉形态、线粒体超微结构和 ROS。结果：结果显示，PDGF-BB 降低了线粒体中 COX5A 的水平并改变了其分布，并降低了复合物 IV 活性、ATP 合成和 OCR，同时增加了 H2O2 合成、ROS 产生以及细胞增殖和迁移。这些影响可通过 COX5A 的过度表达而逆转，并通过 COX5A 敲低而加剧。此外，COX5A 过表达减弱了 BI 诱导的新内膜形成、肌纤维面积比、VSMC 向内膜迁移、线粒体超微结构损伤和血管 ROS 生成。结论：本研究表明，COX5A 通过改善线粒体呼吸功能和减轻线粒体损伤来保护 VSMC 免受表型调节，