Zhang Li, Chen Yingmei, Pan Quanrong, Fang Shizheng, Zhang Zhongjian, Wang Jia, Yang Yongjian, Yang Dachun, Sun Xiongshan
Department of Cardiology, the General Hospital of Western Theater Command, Chengdu 610083, China.
Department of General Practice, the General Hospital of Western Theater Command, Chengdu 610083, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Sep 11;57(4):633-645. doi: 10.3724/abbs.2024154.
The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. , extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying short hairpin RNA (sh ) significantly attenuates NIH and stenosis of the vascular lumen. , small interfering RNA (si )-induced silencing inhibits VSMC proliferation and migration. Additionally, silencing of leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.
血管平滑肌细胞（VSMCs）的病理性增殖和迁移是血管内膜增生（NIH）和再狭窄过程中的关键环节。磷酸烯醇式丙酮酸羧激酶1（PCK1）与多种恶性增殖性疾病密切相关。然而，PCK1在VSMCs中的作用鲜有研究。本研究旨在探讨PCK1在VSMCs增殖、迁移以及损伤后血管NIH中的作用。在损伤动脉中观察到广泛的NIH以及新生内膜中PCK1表达增加。有趣的是，给予携带短发夹RNA（sh）的腺相关病毒9（AAV-9）可显著减轻NIH和血管腔狭窄。此外，小干扰RNA（si）诱导的沉默抑制VSMC增殖和迁移。另外，沉默导致发动蛋白相关蛋白1（DRP1）表达降低以及线粒体分裂减弱。慢病毒介导的DRP1过表达显著逆转沉默对VSMC增殖、迁移和线粒体分裂的抑制作用。最后，PCK1抑制减弱信号转导和转录激活因子3（STAT3）的磷酸化。STAT3激活消除沉默对VSMCs中DRP1表达、线粒体分裂、增殖和迁移的抑制作用。总之，PCK1抑制通过抑制STAT3/DRP1轴减弱VSMCs的线粒体分裂、增殖和迁移，从而抑制血管NIH和再狭窄。
