Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Biochem Biophys Res Commun. 2023 Oct 8;676:30-35. doi: 10.1016/j.bbrc.2023.07.020. Epub 2023 Jul 14.
Long-term cocaine abuse is associated with cardiovascular and pulmonary vascular complications. The vascular toxicity of cocaine can lead to vascular remodeling characterized by excessive proliferation of vascular smooth muscle cells. Though hypoxia-inducible factor (HIF) signaling and mitochondrial fission have been suggested to play essential roles in the pathogenesis of hypoxia-induced vascular remodeling, pathogenetic mechanism for cocaine-related vascular remodeling remains to be elucidated. In this study, we explore the effect of cocaine on the proliferation of vascular smooth muscle cells by in vitro experiments. The findings indicated that the cocaine-induced vascular smooth muscle cell hyperproliferation is achieved by enhancing DRP1-mediated mitochondrial fission and activating PI3K/HIF-1α signaling. Current findings suggested that mitochondrial fission would play a pivotal role in cocaine-related vascular remodeling and would be helpful in understanding the vascular toxicity of cocaine.
长期滥用可卡因与心血管和肺血管并发症有关。可卡因的血管毒性可导致血管重构，其特征是血管平滑肌细胞过度增殖。虽然缺氧诱导因子（HIF）信号和线粒体裂变已被认为在缺氧诱导的血管重构发病机制中起重要作用，但可卡因相关血管重构的发病机制仍有待阐明。在这项研究中，我们通过体外实验探讨了可卡因对血管平滑肌细胞增殖的影响。结果表明，可卡因诱导的血管平滑肌细胞过度增殖是通过增强 DRP1 介导的线粒体裂变和激活 PI3K/HIF-1α 信号来实现的。目前的研究结果表明，线粒体裂变在可卡因相关血管重构中起关键作用，并有助于理解可卡因的血管毒性。
