Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, 41566, South Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu, 41566, South Korea.
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 41566, South Korea.
Biochem Biophys Res Commun. 2021 Jun 30;560:45-51. doi: 10.1016/j.bbrc.2021.04.079. Epub 2021 May 6.
Rapidly proliferating cells such as vascular smooth muscle cells (VSMCs) require metabolic programs to support increased energy and biomass production. Thus, targeting glutamine metabolism by inhibiting glutamine transport could be a promising strategy for vascular disorders such as atherosclerosis, stenosis, and restenosis. V-9302, a competitive antagonist targeting the glutamine transporter, has been investigated in the context of cancer; however, its role in VSMCs is unclear. Here, we examined the effects of blocking glutamine transport in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using V-9302. We found that V-9302 inhibited mTORC1 activity and mitochondrial respiration, thereby suppressing FBS- or PDGF-stimulated proliferation and migration of VSMCs. Moreover, V-9302 attenuated carotid artery ligation-induced neointima in mice. Collectively, the data suggest that targeting glutamine transport using V-9302 is a promising therapeutic strategy to ameliorate occlusive vascular disease.
快速增殖的细胞，如血管平滑肌细胞（VSMCs），需要代谢程序来支持增加的能量和生物量产生。因此，通过抑制谷氨酰胺转运来靶向谷氨酰胺代谢可能是一种有前途的策略，可用于治疗血管疾病，如动脉粥样硬化、狭窄和再狭窄。V-9302 是一种针对谷氨酰胺转运体的竞争性拮抗剂，已在癌症研究中进行了研究；然而，其在 VSMCs 中的作用尚不清楚。在这里，我们使用 V-9302 研究了阻断胎牛血清（FBS）或血小板衍生生长因子（PDGF）刺激的 VSMCs 中的谷氨酰胺转运对 VSMCs 的影响。我们发现，V-9302 抑制了 mTORC1 活性和线粒体呼吸，从而抑制了 FBS 或 PDGF 刺激的 VSMCs 的增殖和迁移。此外，V-9302 减轻了小鼠颈动脉结扎引起的新生内膜。总之，数据表明，使用 V-9302 靶向谷氨酰胺转运是一种有前途的治疗策略，可改善闭塞性血管疾病。
