Snake venom c-type lectin-like protein Vaa-snaclec-3/2 efficiently prevents carotid artery thrombosis in a mouse model without compromising blood coagulation

Žužek, Monika C. (author), Križaj, Igor (author), Brvar, Miran (author), Trobec, Tomaž (author), Kranjc Brezar, Simona (author), Dobaja, Mojca (author), Leonardi, Adrijana (author), Požek, Kity (author), Vrecl, Milka (author), Frangež, Robert (author)

Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom C-type lectin-like protein, mediates this effect ex vivo. Here, we extended our study of the antithrombotic potential of this protein in vivo using a mouse model of ferric chloride (FeCl3)-induced carotid artery thrombosis. Prior to inducing thrombus formation, the mice received 1, 5, 10, 20, or 50 μg/kg Vaa-snaclec-3/2 intravenously. Afterward, the arterial blood flow was monitored with a perivascular Doppler probe. Additionally, the platelet count in the peripheral venous blood; tail bleeding time; and liver, lung, kidney, spleen, and heart histology were evaluated. The lowest dose of Vaa-snaclec-3/2 that we showed to cause severe thrombocytopenia and completely inhibit FeCl3-induced thrombus formation was 20 µg/kg. This dose prolonged the median tail bleeding time from 86.5 to 153.5 s but did not induce acute spontaneous hemorrhage, as demonstrated by histological analysis. Histology revealed no signs of apoptosis, necrosis or other degenerative changes in the inspected organs of mice exposed to 20 μg/kg Vaa-snaclec-3/2. Platelet clusters were observed only in the lungs, which appear to be the primary site of platelet sequestration and the cause of thrombocytopenia. Taken together, our findings highlight the high potential of Vaa-snaclec-3/2 as a safe and effective antithrombotic agent for the transient prevention of thrombosis in acute clinical settings.

• Language: English
• Keywords: snake venom, antithrombotic, snaclec, arterial thrombosis, mice
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 14 str.
• Numbering: Vol. 17, iss. 11, art. 523
• PID: 20.500.12556/RUL-175410
• UDC: 615:616-092:636.09
• ISSN on article: 2072-6651
• DOI: 10.3390/toxins17110523
• COBISS.SI-ID: 254604035
• Publication date in RUL: 20.11.2025

Record is a part of a journal

• Title: Toxins. Elektronski vir
• Shortened title: Toxins
• Publisher: MDPI
• ISSN: 2072-6651
• COBISS.SI-ID: 517594649

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: kačji strup, kače, miši