Enhanced STIM1 expression drives platelet hyperactivity in diabetes

  • Biochem Biophys Res Commun. 2025 Mar 19:753:151510. doi: 10.1016/j.bbrc.2025.151510.
Haoxuan Zhong  1 ,  Maieryemu Waresi  2 ,  Xu Jia  3 ,  Junbo Ge  4
Affiliations
  • 1. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
  • 2. Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3. Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China.
  • 4. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address: [email protected].
PMID: 39986091 DOI: 10.1016/j.bbrc.2025.151510
Abstract

Stromal interaction molecule 1 (STIM1), a key regulator of calcium signaling located in the endoplasmic reticulum, is crucial for platelet function. While elevated STIM1 expression is observed in platelets from diabetic patients, its role in diabetes-induced platelet hyperreactivity remains unclear. In this study, we found a positive correlation between STIM1 expression and agonist-induced platelet aggregation in platelets from patients with type 2 diabetes mellitus (T2DM). Platelets with high STIM1 expression exhibited enhanced aggregation, P-selectin release, Integrin αIIbβ3 activation, spreading, and clot retraction compared to those with low STIM1 expression. Similar findings were observed in db/db mice. Furthermore, the store-operated calcium entry channel inhibitor CM4620 demonstrated superior antiplatelet and antithrombotic efficacy compared to aspirin in both db/db mice and patients with T2DM. Our results suggest that elevated STIM1 expression contributes to enhanced platelet reactivity in diabetes, and targeting STIM1 may offer a promising novel therapeutic approach for thrombosis prevention in this patient population.

Keywords
CM4620; Diabetes; Platelet activation; STIM1.
Products