2. Academic Validation
  3. FKBP5 inhibitor suppresses platelet activation and thrombosis by inhibiting IKBKE/PI3K/Rap1 pathway

FKBP5 inhibitor suppresses platelet activation and thrombosis by inhibiting IKBKE/PI3K/Rap1 pathway

  • Int J Biol Macromol. 2025 Jun;311(Pt 3):144068. doi: 10.1016/j.ijbiomac.2025.144068.
Ziwei Guo 1,  Peijin Li 2,  Zehui Shi 1,  Xuejiao Li 1,  Sixu Bao 2,  Bin Zhong 3,  Ming Zhang 3,  Qiyong Wu 4
Affiliations

Affiliations

  • 1 Graduate School of Dalian Medical University, Dalian 116044, Liaoning Province, China; Department of Cardiothoracic Surgery, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China.
  • 2 Department of Cardiothoracic Surgery, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China; Graduate School of Nanjing Medical University, Nanjing 211166, Jiangsu Province, China.
  • 3 Department of Cardiothoracic Surgery, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China.
  • 4 Department of Cardiothoracic Surgery, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China. Electronic address: wuqiyong1@126.com.
PMID: 40345291 DOI: 10.1016/j.ijbiomac.2025.144068
Abstract

Platelet activation and thrombosis play key roles in Cardiovascular Disease, and the function of FKBP5 in these processes is receiving increasing attention. The study evaluated the potential role of FKBP5 inhibitors in inhibiting platelet activation and thrombosis, and explored the regulation of the IKBKE/PI3K/Rap1 signaling pathway. Bioinformatics analysis, platelet aggregation assay, Lactate Dehydrogenase (LDH) and adenosine triphosphate (ATP) release assay, flow cytometry, Western blot technique, and mesenteric thrombosis model were used to evaluate the effect of FKBP5 inhibitors. Data were analyzed by statistical methods to ensure the reliability of the results. The results showed that FKBP5 inhibitors significantly inhibited platelet aggregation caused by multiple activators and reduced platelet production. Further analysis proved that FKBP5 inhibitors effectively blocked the activation of IKBKE/PI3K/Rap1 signaling pathway. In vivo experiments, FKBP5 inhibitors successfully inhibited mesenteric artery thrombosis, demonstrating its importance in preventing thrombosis, a finding that provides new ideas for the treatment of Cardiovascular Disease.

Keywords

FKBP5 protein molecule; IKBKE/PI3K/Rap1 channel; Inhibitor; Platelet activation; Thrombosis.

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