2. Academic Validation
  3. Intervention of asprosin attenuates oxidative stress and neointima formation in vascular injury

Intervention of asprosin attenuates oxidative stress and neointima formation in vascular injury

  • Antioxid Redox Signal. 2024 May 30. doi: 10.1089/ars.2023.0383.
Fen Zheng 1,  Chao Ye 2,  Jian-Zhen Lei 3,  Rui Ge 4,  Na Li 5,  Jin-Hua Bo 6,  Ai-Dong Chen 7,  Feng Zhang 8,  Hong Zhou 9,  Jue-Jin Wang 10,  Qi Chen 11,  Yue-Hua Li 12,  Guo-Qing Zhu 13,  Ying Han 14
Affiliations

Affiliations

  • 1 Nanjing Medical University, Nanjing, Jiangsu, China; fenzh@njmu.edu.cn.
  • 2 Nanjing Medical University, Nanjing, Jiangsu, China; yechao@jiangnan.edu.cn.
  • 3 Nanjing Medical University, Nanjing, Jiangsu, China; leijianzhenok@163.com.
  • 4 Nanjing Medical University, Nanjing, Jiangsu, China; gerui@njmu.edu.cn.
  • 5 Nanjing Medical University, Nanjing, Jiangsu, China; nali@njmu.edu.cn.
  • 6 Nanjing Medical University, Nanjing, Jiangsu, China; bojinhua@njglyy.com.
  • 7 Nanjing Medical University, Nanjing, Jiangsu, China; aidongchen@njmu.edu.cn.
  • 8 Nanjing Medical University, Nanjing, Jiangsu, China; fengzhang@njmu.edu.cn.
  • 9 Nanjing Medical University, Nanjing, Jiangsu, China; hongzhou@njmu.edu.cn.
  • 10 Nanjing Medical University, Nanjing, Jiangsu, China; juejinwang@njmu.edu.cn.
  • 11 Nanjing Medical University, Nanjing, Jiangsu, China; qichen@njmu.edu.cn.
  • 12 Nanjing Medical University, Pathophysiology, Nanjing, Jiangsu, China; yhli@njmu.edu.cn.
  • 13 Nanjing Medical University, Nanjing, Jiangsu, China; gqzhucn@njmu.edu.cn.
  • 14 Nanjing Medical University, Nanjing, Jiangsu, China; yhancn@njmu.edu.cn.
PMID: 38814824 DOI: 10.1089/ars.2023.0383
Abstract

Aims: Asprosin, a newly discovered hormone, is linked to Insulin resistance. This study shows the roles of asprosin in vascular smooth muscle cells (VSMCs) proliferation, migration, oxidative stress and neointima formation of vascular injury.

Methods: Mouse aortic VSMCs were cultured, and platelet-derived growth factor-BB (PDGF-BB) was used to induce oxidative stress, proliferation and migration in VSMCs. Vascular injury was induced by repeatedly moving a guidewire in the lumen of carotid artery in mice.

Results: Asprosin overexpression promoted VSMC oxidative stress, proliferation and migration, which were attenuated by Toll-like Receptor 4 (TLR4) knockdown, antioxidant NAC, NOX1 Inhibitor ML171 or NOX2 Inhibitor GSK2795039. Asprosin overexpression increased NOX1/2 expressions, while asprosin knockdown increased heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions. Asprosin inhibited Nrf2 nuclear translocation. Nrf2 activator sulforaphane increased HO-1 and NQO-1 expressions, and prevented asprosin-induced NOX1/2 upregulation, oxidative stress, proliferation and migration. Exogenous asprosin protein had similar roles to asprosin overexpression. PDGF-BB increased asprosin expressions. PDGF-BB-induced oxidative stress, proliferation and migration were enhanced by Nrf2 inhibitor ML385, but attenuated by asprosin knockdown. Vascular injury increased asprosin expression. Local asprosin knockdown in the injured carotid artery promoted HO-1 and NQO-1 expressions, but attenuated the NOX1 and NOX2 upregulation, oxidative stress, neointima formation and vascular remodeling in mice.

Innovation and conclusion: Asprosin promotes oxidative stress, proliferation and migration of VSMCs via TLR4-Nrf2-mediated redox imbalance. Inhibition of asprosin expression attenuates VSMC proliferation and migration, oxidative stress and neointima formation in the injured artery. Asprosin might be a promising therapeutic target for vascular injury.

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