Laminar shear stress inhibits endothelial-mesenchymal transition and mitigates atherosclerosis through SRXN1

  • Atherosclerosis. 2026 Jul:418:120789. doi: 10.1016/j.atherosclerosis.2026.120789.
Xingyu Jiang  1 ,  Qingyu Meng  2 ,  Luya Pu  2 ,  Shuai Li  2 ,  Banghao Sun  3 ,  Bin Liu  4 ,  Fan Li  5
Affiliations
  • 1. Department of Pathogen Biology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
  • 2. China-Japan Union Hospital of Jilin University, Changchun, China.
  • 3. Jilin Province Institute of Cancer Prevention and Treatment, Jilin Province Cancer Hospital, Changchun, China.
  • 4. Cardiovascular Disease Center, The First Hospital of Jilin University, Changchun, China. Electronic address: [email protected].
  • 5. Department of Pathogen Biology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China; The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun, China; Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun, China; Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang China. Electronic address: [email protected].
PMID: 42202676 DOI: 10.1016/j.atherosclerosis.2026.120789
Abstract

Background and aims: Atherosclerosis (AS), a critical inflammatory condition of the arteries that leads to cardiovascular diseases, has a complex pathophysiological mechanism involving multifactorial interactions. Endothelial-mesenchymal transition (EndMT) is considered an important factor promoting AS. Laminar shear stress (LSS) has a pivotal function in regulating AS and EndMT processes; however, its specific mechanisms remain unknown.

Methods: We analyzed the transcriptomic and proteomic data of human aortic endothelial cells (HAECs) in static culture and subjected to LSS treatment and identified a key gene, namely sulfiredoxin-1 (SRXN1), closely associated with AS progression. To understand how SRXN1 influences EndMT and AS and the potential underlying mechanisms, we conducted an in vitro flow chamber study with HAECs and an in vivo study with AS model mice.

Results: Our results indicated that LSS alleviated oxidized low-density lipoprotein (ox-LDL)-induced EndMT in HAECs. Transcriptome and proteome Sequencing analyses showed that SRXN1 functions as a key gene in LSS-treated endothelial cells; moreover, in HAECs, LSS remarkably suppressed ox-LDL-induced inflammation, oxidative stress, and EndMT, and this protective effect was substantially attenuated by SRXN1 knockdown. Additionally, SRXN1 overexpression reversed ox-LDL-induced inflammation and oxidative stress as well as EndMT. In vivo studies revealed that endothelial-specific adeno-associated virus overexpressing SRXN1 (AAV9-SRXN1) administered through the tail vein significantly suppressed aortic plaque development and EndMT in high-fat diet-induced apoE-/- mice.

Conclusions: Our data demonstrate that LSS through SRXN1 upregulation inhibits oxidative stress and prevents EndMT progression, thereby maintaining endothelial homeostasis and suppressing atherosclerotic progression.

Keywords
Atherosclerosis; EndMT; Endothelial cells; Laminar shear stress; SRXN1.
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