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.

血管平滑肌细胞 (VSMC) 等快速增殖的细胞需要代谢程序来支持增加的能量和生物量生产。因此，通过抑制谷氨酰胺转运来靶向谷氨酰胺代谢可能是治疗动脉粥样硬化、狭窄和再狭窄等血管疾病的有前途的策略。 V-9302 是一种针对谷氨酰胺转运蛋白的竞争性拮抗剂，已在癌症方面进行了研究；然而，其在 VSMC 中的作用尚不清楚。在这里，我们使用 V-9302 检测了在胎牛血清 (FBS) 或血小板衍生生长因子 (PDGF) 刺激的 VSMC 中阻断谷氨酰胺转运的效果。我们发现 V-9302 抑制 mTORC1 活性和线粒体呼吸，从而抑制 FBS 或 PDGF 刺激的 VSMC 增殖和迁移。此外，V-9302 还可减轻小鼠颈动脉结扎诱导的新内膜。总的来说，数据表明，使用 V-9302 靶向谷氨酰胺转运是改善闭塞性血管疾病的一种有前景的治疗策略。