Unfractionated Heparin Enhances Sepsis Prognosis Through Inhibiting Drp1‐Mediated Mitochondrial Quality Imbalance
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.
Authors
- Yu Tian (ORCID: https://orcid.org/0000-0002-1462-7280)
- Liangming Liu (ORCID: https://orcid.org/0000-0001-6001-8729)
- Shuai Hao (ORCID: https://orcid.org/0000-0003-4942-2215)
- Dongyao Hou
- Qiao Guo (ORCID: https://orcid.org/0000-0002-3589-4599)
- Chenyang Duan (ORCID: https://orcid.org/0000-0002-6081-5987)
- Rui Song (ORCID: https://orcid.org/0000-0003-1875-2115)
- He Huang (ORCID: https://orcid.org/0000-0001-9307-871X)
- Qian Chen (ORCID: https://orcid.org/0000-0002-1909-302X)
- Daqing Ma (ORCID: https://orcid.org/0000-0003-1235-0537)
- Ruixue Liu (ORCID: https://orcid.org/0000-0001-9478-5993)
- Haitang Liao
- Zhenchun Luo
Institutions
- Hubei University of Medicine (CN)
- Army Medical University (CN)
- Dalian Medical University (CN)
- Nanjing General Hospital of Nanjing Military Command (CN)
- Daping Hospital (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Children's Hospital of Zhejiang University (CN)
- Taihe Hospital (CN)
- Chelsea and Westminster Hospital (GB)
- First People's Hospital of Chongqing (CN)
- Imperial College London (GB)
- Nanjing Medical University (CN)
- Chongqing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1002/advs.202407705
- Citations
- 5
- Primary Topic
- Sepsis Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.93
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Chongqing