Sulforaphane prevents abdominal aortic aneurysm formation through the inhibition of phenotypic switching of vascular smooth muscle cells and inflammation via the activation of Nrf2

  • Cell Signal. 2026 Aug:144:112527. doi: 10.1016/j.cellsig.2026.112527.
Zhenhua Huang  1 ,  Yu Tao  2 ,  Cheng Liu  3 ,  Junfen Wang  4 ,  Cong Deng  5 ,  Zhiyuan Han  3 ,  Tianchan Yun  5 ,  Tian Li  6 ,  Weiling Lu  7 ,  Yanxian Lai  8
Affiliations
  • 1. Department of Emergency Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 1 Panfu road, Guangzhou 510180, China.
  • 2. Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, 92 Aiguo Road, Donghu, Nanchang, Jiangxi 330006, PR China.
  • 3. Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology, China; Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu road, Guangzhou 510180, China.
  • 4. Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 5. Guangzhou First People's Hospital, South China University of Technology, China; Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu road, Guangzhou 510180, China.
  • 6. Tianjin Nankai Hospital, Tianjin Medical University, 8 Changjiang Avenue, Tianjin 300100, China. Electronic address: [email protected].
  • 7. Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Department of Cardiology, Guangdong Provincial People's Hospital Ganzhou Hospital, Ganzhou Municipal Hospital (Gannan Medical University Afliated Municipal Hospital), 49 Dagong Road, 341000 Ganzhou, China. Electronic address: [email protected].
  • 8. Department of Cardiology, Guangzhou First People's Hospital, South China University of Technology, China; Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu road, Guangzhou 510180, China; Department of Geriatrics, Guangzhou Chest Hospital, Guangdong Pharmaceutical University, Guangzhou 510180, China.. Electronic address: [email protected].
PMID: 41941990 DOI: 10.1016/j.cellsig.2026.112527
Abstract

Objective: Targeted therapy for the phenotypic switching of vascular smooth muscle cell(VSMC) is a critical strategy for mitigating disease progression in patients with abdominal aortic aneurysms (AAAs). Sulforaphane (SFN), a nuclear factor E2 factor-related factor (Nrf2) activator, has anti-inflammatory and antioxidant properties and might regulate the phenotypic switching of VSMCs. However, the role of SFN in AAA formation is unknown. In this study, we explored the inhibitory effect of SFN on AAA formation and its underlying mechanisms.

Methods: Quantitative PCR, western blotting and immunohistochemistry were used to determine biomarkers of the contractile state of VSMC expression and proinflammatory factor expression in cell and mouse AAA samples. SFN treatment and Nrf2 knockout were performed to investigate the role of SFN in AAA formation. In vivo VSMC Nrf2 conditional knockout experiments were performed to determine the critical role of Nrf2 in the protective effect of SFN on AAA.

Results: SFN alleviated AAA formation and inhibited VSMC phenotype switching and vascular inflammation. Mechanistically, SFN retained the contractile state of VSMCs and inhibited inflammation via the activation of Nrf2. Moreover, Nrf2 deficiency significantly counteracted the protective effect of SFN in inhibiting VSMC phenotype switching and macrophage activation, thereby promoting AAA formation.

Conclusion: SFN inhibited AAA formation by suppressing VSMC phenotype switching and vascular inflammation. SFN is a potential effective treatment for AAA.

Keywords
Abdominal aortic aneurysm; Inflammation; Nuclear factor E2 factor-related factor (Nrf2); Sulforaphane (SFN); Vascular smooth muscle cell phenotype switching.
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