期刊
EXPERIMENTAL AND THERAPEUTIC MEDICINE
卷 19, 期 6, 页码 3454-3460出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2020.8638
关键词
vascular smooth muscle cells; melatonin; Sestrin2; proliferation; apoptosis
资金
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF 2017M3A9G7073086, NRF-2018R1A2A1A05077703]
- NRF - Ministry of Education [NRF-2017R1A6A3A04010231]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Ministry of Health and Welfare, Republic of Korea [HI16C1501, HI15C0001]
- National Research Foundation of Korea [2017M3A9G7073086] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Excessive vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis and restenosis. Furthermore, apoptosis of VSMCs accelerates plaque rupture in the atherosclerotic vessels. Therefore, a strategy that regulates both VSMC proliferation and apoptosis is essential for the development of novel pharmacological tools for the treatment of atherosclerosis. Despite mounting evidence supporting the benefits of melatonin in diverse metabolic diseases, the role of melatonin in VSMC growth remains largely unknown. The present study revealed that melatonin inhibited both proliferation and apoptosis of primary cultured rat VSMCs. Melatonin induced mitochondrial energetic stress in VSMCs and subsequent induction of Sestrin2 via C/EBP beta. Melatonin-induced Sestrin2 suppressed mTORC1 activity in VSMCs, contributing to suppression of VSMC proliferation. Additionally, melatonin-induced upregulation of Sestrin2 blocked apoptosis by preventing excessive ROS generation. The results demonstrated that melatonin controlled VSMC proliferation and apoptosis via Sestrin2-mediated inhibition of mTORC1 and ROS scavenging. Therefore, melatonin should be considered as a lead compound for therapies aimed at preventing vessel lumen constriction during the course of atherosclerosis and restenosis.
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