2. Academic Validation
  3. HIIT and MICT mitigate endothelial dysfunction in early atherosclerotic mice via PCSK9 inhibition

HIIT and MICT mitigate endothelial dysfunction in early atherosclerotic mice via PCSK9 inhibition

  • Sci Rep. 2025 Aug 19;15(1):30411. doi: 10.1038/s41598-025-05206-7.
Guochun Liu 1 2 3,  Binyi Zhao 4,  Qinglong Chen 1 5,  Xiang Li 1 5,  Xuejiao Zhu 1 5,  Maowei Duan 1 5,  Mengdie Zhang 1 5,  Zhuohan Liu 1 6,  Xuan Wen 3,  Jia Guo 3,  Man Zheng 3,  Ruiyu Wang 7,  Minghao Luo 8 9
Affiliations

Affiliations

  • 1 Chongqing Medical University, Chongqing, China.
  • 2 The College of Exercise Medicine, Chongqing Medical University, Chongqing, China.
  • 3 Division of Sports Science and Physical Education, Tsinghua University, Beijing, China.
  • 4 First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
  • 5 College of Basic Medicine, Chongqing Medical University, Chongqing, China.
  • 6 College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China.
  • 7 Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. wangruiyu@med.uestc.edu.cn.
  • 8 Chongqing Medical University, Chongqing, China. luominghao001@hospital.cqmu.edu.cn.
  • 9 Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. luominghao001@hospital.cqmu.edu.cn.
PMID: 40830352 DOI: 10.1038/s41598-025-05206-7
Abstract

Atherosclerosis (AS), driven by vascular endothelial dysfunction and poses a global health threat. This study compared the therapeutic effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on vascular endothelial function in early-stage AS mice, specifically investigating PCSK9 modulation and the TRX/TXNIP/NLRP3/GSDMD-N pathway. apoE-/- mice (n = 6/group) fed a high-fat diet for 12 weeks were randomized into sedentary (AS-S), HIIT (AS-HIIT), and MICT (AS-MICT) groups, with wild-type mice as control. Training lasted 12 weeks. Outcomes included body weight, lipid profiles (TG, TC, LDL-C, HDL-C), oxidative stress markers (T-SOD, GSH-Px, MDA), vascular function (eNOS expression, ACh-induced vasorelaxation), and TRX/TXNIP/NLRP3/GSDMD-N pathway activity. Both HIIT and MICT reduced body weight (p < 0.05) and improved lipid profile. Exercise groups showed reduced oxidative stress and inflammation pathways (p < 0.05). HIIT and MICT ameliorate early AS by reducing PCSK9 and oxidative/inflammatory pathway levels (p < 0.05), but HIIT demonstrates superior efficacy in improving endothelial function and pathway activation. These findings show HIIT and MICT mitigate endothelial dysfunction in early atherosclerotic mice via PCSK9 inhibition and advocate for HIIT as a prioritized strategy in early AS management.

Keywords

Atherosclerosis; Endothelial dysfunction; Exercise; Pyroptosis.

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