2. Academic Validation
  3. Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles alleviates atherosclerosis by suppressing macrophage ferroptosis via the NRF2/SLC7A11/GPX4 pathway

Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles alleviates atherosclerosis by suppressing macrophage ferroptosis via the NRF2/SLC7A11/GPX4 pathway

  • Arch Biochem Biophys. 2025 Mar:765:110316. doi: 10.1016/j.abb.2025.110316.
Mengying Jin 1,  Xiao Chen 2,  Lanzhuoying Zheng 3,  Yuanyuan Peng 4,  Mingying Lin 5,  Ke Liang 6,  Xinran Liu 7,  Zihan Xu 8,  Yiming Yang 9,  Baozhu Wei 10,  Jing Wan 11
Affiliations

Affiliations

  • 1 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 2017302180262@whu.edu.cn.
  • 2 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 2019305232008@whu.edu.cn.
  • 3 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 865546617@qq.com.
  • 4 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: pengyy@whu.edu.cn.
  • 5 Department of Cardiology, Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China. Electronic address: linliavia@outlook.com.
  • 6 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 303516390@qq.com.
  • 7 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 503137332@qq.com.
  • 8 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 2020305233148@whu.edu.cn.
  • 9 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: 17339304090@163.com.
  • 10 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: wbz9810@163.com.
  • 11 Department of Cardiology, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China. Electronic address: wanjing_zn@163.com.
PMID: 39848420 DOI: 10.1016/j.abb.2025.110316
Abstract

Background: Astaxanthin (ASX), a fat-soluble carotenoid mainly sourced from Haematococcus pluvialis, shows promise for clinical applications in chronic inflammatory diseases. This study investigates whether ASX can mitigate atherosclerosis (AS) by modulating macrophage Ferroptosis and provides astaxanthin-loaded polylactic acid-glycolic acid nanoparticles (ASX-PLGA NPs) as comparison.

Method: ApoE-/- mice were fed a high-fat diet with ASX or statin intervention. Plaque area, lipid aggregation, collagen content, and ferroptosis-related indicators were assessed. Moreover, ASX-PLGA NPs were synthesized and characterized and were used to pretreat macrophages induced with oxidized low-density lipoprotein (ox-LDL). Indicators linked to Ferroptosis and oxidative stress were detected. Finally, the expression of nuclear factor erythroid -related factor 2 (NRF2) was evaluated.

Results: ASX intervention significantly delayed the progression of AS plaques, characterized by reductions in plaque area and increased collagen fibers. The observed improvements in AS were consistent with statins. ASX-PLGA NPs demonstrate good safety and stability and have better therapeutic effects than ASX alone. Indicators linked to Ferroptosis and oxidative stress were significantly improved in groups containing ASX in vivo and vitro. Additionally, ASX facilitated the nuclear translocation of NRF2, which could be attenuated with ML385, a specific inhibitor of NRF2.

Conclusion: ASX-PLGA NPs have better therapeutic effects than ASX alone. The regulation of NRF2/SLC7A11/GPX4 represents a novel mechanism by which ASX can counteract Ferroptosis and impede AS progression.

Keywords

Astaxanthin; Atherosclerosis; Ferroptosis; NRF2; Oxidative stress; PLGA NPs.

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