Unfractionated Heparin Enhances Sepsis Prognosis Through Inhibiting Drp1‐Mediated Mitochondrial Quality Imbalance
Year: 2024
Type: article
Abstract: Unfractionated heparin (UFH) is commonly used as an anticoagulant in sepsis treatment and has recently been found to have non-anticoagulant effects, but underlying mechanisms remain unclear. This retrospective clinical data showed that UFH has significant protective effects in sepsis compared to low-molecular-weight heparin and enoxaparin, indicating potential benefits of its non-anticoagulant properties. Recombinant protein chip screening, surface plasmon resonance, and molecular docking data demonstrated that UFH specifically bound to the cytoplasmic Drp1 protein through its zone 2 non-anticoagulant segment. In-vitro experiments verified that UFH's specific binding to Drp1 suppressed Drp1 translocation to mitochondria following "sepsis" challenge, thereby improving mitochondrial morphology, function and metabolism in vascular endothelial cells. Consequently, UHF comprehensively protected mitochondrial quality, thus reducing vascular leakage and improving prognosis in a sepsis rat model. These findings highlight the potential of UFH as a sepsis treatment strategy targeting non-anticoagulation mechanism.
Source: Advanced Science
Authors: Ruixue Liu, He Huang, Dongyao Hou, Shuai Hao, Qiao Guo, Haitang Liao, Rui Song, Yu Tian, Qian Chen, Zhenchun Luo, Daqing Ma, Liangming Liu, Chenyang Duan
Institutions: Second Affiliated Hospital of Chongqing Medical University, Hubei University of Medicine, Taihe Hospital, Nanjing General Hospital of Nanjing Military Command, Nanjing University, Children's Hospital of Zhejiang University, Zhejiang University, Chelsea and Westminster Hospital, Imperial College London, Army Medical University, Daping Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,120
OpenAlex ID: W4403709372