2. Academic Validation
  3. The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice

The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice

  • Nat Cardiovasc Res. 2025 Feb;4(2):216-234. doi: 10.1038/s44161-025-00613-5.
Xuan Wang # 1,  Mi Wang # 2 3 4,  Tian-Tian Zhu 1,  Zi-Jie Zheng 1,  Shuang Li 1,  Zhao-Yi Sui 1,  Xin Guo 2,  Sha Wu 2,  Nai-Ning Zhang 5,  Zhi-Yi Yu 5,  Chang-Ping Hu 1 6,  Yong-Bo Tang 7,  Qing Wang 8,  Zheng Zhang 9 10
Affiliations

Affiliations

  • 1 Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
  • 2 Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 3 Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, China.
  • 4 Hunan Key Laboratory of Cardiometabolic Medicine, Central South University, Changsha, China.
  • 5 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 6 Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, China.
  • 7 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
  • 8 Department of Interventional Radiology & Vascular Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
  • 9 Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China. zzhang@csu.edu.cn.
  • 10 Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, China. zzhang@csu.edu.cn.
  • # Contributed equally.
PMID: 39953275 DOI: 10.1038/s44161-025-00613-5
Abstract

Ionic signaling in smooth muscle cells (SMCs) is critical for vascular homeostasis. In this study, we untangled the role of the bifunctional TRPM7 channel kinase (chanzyme) in abdominal aortic aneurysm (AAA) pathogenesis. Comparing SMC-specific, macrophage-specific and endothelial cell-specific Trpm7 knockout, we revealed that SMC-specific Trpm7 deficiency protected mice from AAA in two distinct preclinical models of the disease. We showed that the TRPM7 channel activity increased the CA2+ and Zn2+ influx and the CA2+/Calcineurin/CRTC2/CREB-dependent and Zn2+/MTF1-dependent Mmp2 transcription. Repurposing the clinical drug FTY720 to prevent and treat AAA resulted in improved aortic phenotypes through inhibition of TRPM7 channel activity. This study highlights the ionic mechanisms underlying AAA, identifies TRPM7 as a potential therapeutic target and suggests that blocking TRPM7 channels could be a viable strategy for treating AAA.

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