Open Access

Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2

  • Authors:
    • Seunghyeong Lee
    • Jun‑Kyu Byun
    • Mihyang Park
    • Sung Woo Kim
    • Sungwoo Lee
    • Jung‑Guk Kim
    • In‑Kyu Lee
    • Yeon‑Kyung Choi
    • Keun‑Gyu Park
  • View Affiliations

  • Published online on: April 2, 2020     https://doi.org/10.3892/etm.2020.8638
  • Pages: 3454-3460
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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/EBPβ. 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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June-2020
Volume 19 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Lee S, Byun JK, Park M, Kim S, Lee S, Kim JG, Lee IK, Choi YK and Park KG: Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2. Exp Ther Med 19: 3454-3460, 2020
APA
Lee, S., Byun, J., Park, M., Kim, S., Lee, S., Kim, J. ... Park, K. (2020). Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2. Experimental and Therapeutic Medicine, 19, 3454-3460. https://doi.org/10.3892/etm.2020.8638
MLA
Lee, S., Byun, J., Park, M., Kim, S., Lee, S., Kim, J., Lee, I., Choi, Y., Park, K."Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2". Experimental and Therapeutic Medicine 19.6 (2020): 3454-3460.
Chicago
Lee, S., Byun, J., Park, M., Kim, S., Lee, S., Kim, J., Lee, I., Choi, Y., Park, K."Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2". Experimental and Therapeutic Medicine 19, no. 6 (2020): 3454-3460. https://doi.org/10.3892/etm.2020.8638