1. V-9302 inhibits proliferation and migration of VSMCs, and reduces neointima formation in mice after carotid artery ligation
- Author
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Jonghwa Jin, Seunghyeong Lee, Mi Jin Kim, Ye Jin Kim, Keun-Gyu Park, Sungwoo Lee, Yeon-Kyung Choi, and Hyeon Young Park
- Subjects
Male ,0301 basic medicine ,Neointima ,Vascular smooth muscle ,Amino Acid Transport System A ,medicine.medical_treatment ,Cell Respiration ,Biophysics ,Context (language use) ,Mechanistic Target of Rapamycin Complex 1 ,Pharmacology ,Biochemistry ,Muscle, Smooth, Vascular ,Glutamine transport ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,Ligation ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,Platelet-Derived Growth Factor ,biology ,Chemistry ,Growth factor ,Cell Cycle ,Serum Albumin, Bovine ,Cell Biology ,Mitochondria ,Mice, Inbred C57BL ,Glutamine ,Carotid Arteries ,030104 developmental biology ,030220 oncology & carcinogenesis ,cardiovascular system ,biology.protein ,Platelet-derived growth factor receptor ,Fetal bovine serum - Abstract
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.
- Published
- 2021