ShSPI Inhibits Thrombosis Formation and Ischemic Stroke In Vivo

Thrombotic diseases, emerging as a global public health hazard with high mortality and disability rates, pose a significant threat to human health and longevity. Although current antithrombotic therapies are effective in treating these conditions, they often carry a substantial risk of bleeding, hig...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-08, Vol.25 (16), p.9003
Main Authors: Luan, Ning, Cao, Han, Wang, Yunfei, Zhang, Haihao, Lin, Kangyang, Hu, Jingping, Rong, Mingqiang, Liu, Cunbao
Format: Article
Language:English
Subjects:
Animals
Anticoagulants
Blood clots
Blood platelets
Carrageenan
Cytotoxicity
Disease Models, Animal
elastase inhibitor
Fibrinolytic Agents - pharmacology
Fibrinolytic Agents - therapeutic use
Investigations
Ischemia
ischemic stroke
Ischemic Stroke - drug therapy
Ischemic Stroke - metabolism
Ischemic Stroke - pathology
Male
Mice
Mice, Inbred C57BL
Nitric Oxide Synthase Type III - metabolism
Oxidative stress
ShSPI
Superoxide Dismutase - metabolism
Thrombosis
Thrombosis - drug therapy
thrombotic diseases
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Summary:Thrombotic diseases, emerging as a global public health hazard with high mortality and disability rates, pose a significant threat to human health and longevity. Although current antithrombotic therapies are effective in treating these conditions, they often carry a substantial risk of bleeding, highlighting the urgent need for safer therapeutic alternatives. Recent evidence has increasingly pointed to a connection between elastase activity and thrombosis. In the current study, we investigated the antithrombotic effects of ShSPI, an elastase inhibitor peptide derived from the venom of . Results showed that ShSPI significantly attenuated carrageenan-induced thrombosis in vivo. Furthermore, ShSPI effectively inhibited the carrageenan-induced decrease in serum superoxide dismutase (SOD) activity and increase in prothrombin time, fibrinogen level, and endothelial nitric oxide synthase (eNOS) activity. In addition, ShSPI reduced intracerebral thrombosis and improved functional outcomes following ischemic stroke in a transient middle cerebral artery occlusion (tMCAO) mouse model. Collectively, these findings suggest that ShSPI is a promising candidate for the development of novel thrombotic therapies.
ISSN:1661-6596
1422-0067
1422-0067
DOI:10.3390/ijms25169003