Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke
Basic science / preclinical published in Cell Mol Life Sci (2022)
Abstract
Ischemic stroke is a leading cause of death and disability worldwide. Increasing evidence indicates that ischemic stroke is a thromboinflammatory disease in which the contact-kinin pathway has a central role by activating pro-coagulant and pro-inflammatory processes. The blocking of distinct members of the contact-kinin pathway is a promising strategy to control ischemic stroke. Here, a plasma kallikrein and active FXII (FXIIa) inhibitor (sylvestin, contained 43 amino acids, with a molecular weight of 4790.4 Da) was first identified from forest leeches (Haemadipsa sylvestris). Testing revealed that sylvestin prolonged activated partial thromboplastin time without affecting prothrombin time. Thromboelastography and clot retraction assays further showed that it extended clotting time in whole blood and inhibited clot retraction in platelet-rich plasma. In addition, sylvestin prevented thrombosis in vivo in FeCl3-induced arterial and carrageenan-induced tail thrombosis models. The potential role of sylvestin in ischemic stroke was evaluated by transient and permanent middle cerebral artery occlusion models. Sylvestin administration profoundly protected mice from ischemic stroke by counteracting intracerebral thrombosis and inflammation. Importantly, sylvestin showed no signs of bleeding tendency. The present study identifies sylvestin is a promising contact-kinin pathway inhibitor that can proffer profound protection from ischemic stroke without increased risk of bleeding.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Identification of sylvestin, a 43-aa contact-kinin inhibitor from forest leeches Haemadipsa sylvestris. Inhibits plasma kallikrein and FXIIa, prolongs APTT, reduces thrombosis in FeCl/carrageenan models, and protects against ischemic stroke without bleeding tendency.
Why This Matters for Hirudotherapy
This study identified sylvestin, a 43-amino-acid (4,790.4 Da) plasma kallikrein and FXIIa inhibitor from forest leeches (Haemadipsa sylvestris), as a novel contact-kinin pathway inhibitor. Sylvestin prolonged aPTT without affecting PT, extended clotting time in whole blood, inhibited clot retraction, prevented thrombosis in FeCl3-induced arterial and carrageenan-induced tail models, and profoundly protected mice from ischemic stroke in transient and permanent MCAO models without bleeding tendency. For ASH's domain, this is directly relevant: sylvestin is a novel antithrombotic/anti-thromboinflammatory molecule isolated from a leech species, expanding the pharmacological repertoire of leech-derived compounds. Caveat: this is preclinical (mouse models); no human data, formulation, or clinical testing is presented; the abstract reports no bleeding signs in animal models, but human safety and efficacy remain unestablished.
Citation
Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke.
Zhang Z et al. · Cellular and molecular life sciences, 2022
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