Projects / Programmes
Reversibility of transient thrombocytopenia induced by a snake venom component offers a safe antithrombotic prevention in interventional angiology and cardiology
Code |
Science |
Field |
Subfield |
3.06.00 |
Medical sciences |
Cardiovascular system |
|
Code |
Science |
Field |
3.02 |
Medical and Health Sciences |
Clinical medicine |
Transient thrombocytopenia; Functional platelets; Snaclec; Antiplatelet drug; Antiaggregants, Hemorrhage
Researchers (19)
no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
1. |
15595 |
Katarina Babnik |
|
Technical associate |
2020 - 2023 |
8 |
2. |
24927 |
PhD Miran Brvar |
Neurobiology |
Head |
2020 - 2023 |
609 |
3. |
38536 |
Mojca Dobaja |
Public health (occupational safety) |
Researcher |
2020 - 2023 |
46 |
4. |
18122 |
Boštjan Drolc |
Veterinarian medicine |
Technical associate |
2020 - 2023 |
10 |
5. |
12449 |
PhD Robert Frangež |
Veterinarian medicine |
Researcher |
2020 - 2023 |
289 |
6. |
37918 |
Damjan Grenc |
Neurobiology |
Researcher |
2020 - 2023 |
136 |
7. |
50498 |
PhD Adrijan Ivanušec |
Biochemistry and molecular biology |
Researcher |
2021 - 2023 |
28 |
8. |
55063 |
Špela Koren |
Biochemistry and molecular biology |
Junior researcher |
2021 - 2023 |
23 |
9. |
00412 |
PhD Igor Križaj |
Biochemistry and molecular biology |
Researcher |
2020 - 2023 |
740 |
10. |
18802 |
PhD Adrijana Leonardi |
Biochemistry and molecular biology |
Researcher |
2020 - 2023 |
162 |
11. |
56248 |
Leja Perne |
Biochemistry and molecular biology |
Technical associate |
2022 - 2023 |
13 |
12. |
20213 |
PhD Toni Petan |
Biochemistry and molecular biology |
Researcher |
2020 - 2023 |
182 |
13. |
04570 |
PhD Jože Pungerčar |
Biochemistry and molecular biology |
Researcher |
2020 - 2023 |
320 |
14. |
18125 |
Jasna Šporar |
|
Technical associate |
2020 - 2023 |
0 |
15. |
21553 |
PhD Jernej Šribar |
Biochemistry and molecular biology |
Researcher |
2020 - 2023 |
114 |
16. |
07002 |
PhD Dušan Šuput |
Neurobiology |
Researcher |
2020 - 2023 |
436 |
17. |
13334 |
PhD Milka Vrecl Fazarinc |
Veterinarian medicine |
Researcher |
2020 - 2023 |
273 |
18. |
56000 |
Mia Žganjar |
Biochemistry and molecular biology |
Researcher |
2021 - 2023 |
13 |
19. |
22588 |
PhD Monika Cecilija Žužek |
Veterinarian medicine |
Researcher |
2020 - 2023 |
74 |
Organisations (4)
Abstract
In thromboembolic diseases, such as myocardial infarction and ischemic stroke, platelets play a pivotal role. Currently used antiplatelet drugs have one common side effect – a decreased count of platelets with inhibited function. Such condition represents a high risk of life-threatening hemorrhage especially in interventional cardiology and angiology employing antithrombotic approach. Recently, we reported an interesting observation of a profound and transient thrombocytopenia of functional platelets in patients bitten by the nose-horned viper (Vipera ammodytes ammodytes, Vaa), revealing that the Vaa venom contains component(s) that can transiently decrease platelets count without affecting their function. In this project, we will comprehensively describe this antithrombotic substance(s) and its mode of action thus paving the way to development of a new group of antiplatelet agents, which will minimize the risk of life-threatening bleeding in antithrombotic approach in interventional cardiology and angiology, and increase the effectiveness of vessel dilatation and emboli aspiration. Based on our preliminary data, we suggest that snake C-type lectin-like proteins (snaclecs) induce transient and reversible thrombocytopenia in the Vaa venom-poisoned patients by binding to GPIb receptors on platelets. The Vaa snaclecs are proteins of 25–50 kDa. They apper as heterodimers formed from an ? subunit of 14–15 kDa and a ß subunit of 13–14 kDa held together by an inter-chain disulphide bond, and their dimeric form – (?ß)2. The scientific challenge that the proposed project is tackling requires a multidisciplinary approach, clinical, pharmacological, pathophysiological, biochemical and immunological, at the clinical, preclinical as well as basic research levels. Project team gathers experts with required complementary skills and equipment from the University Medical Centre Ljubljana, Jožef Stefan Institute, Veterinary and Medical faculties of the University of Ljubljanaand University of Zagreb - an external partner, which all successfully collaborated in the past, with a strictly defined role in the project. The four main goals that we are pursuing in the proposed project are: (1) to identify whether the Vaa snaclecs induce thrombocytopenia in patients envenomed by the Vaa venom by reversibly attaching platelets to the blood vessel wall or by reversible aggregation of platelets; (2) to purify snaclecs from the Vaa venom and biochemically characterize them in depth; (3) to define the molecular basis of the interaction of the Vaa snaclecs with platelets, a process behind a transient and reversible thrombocytopenia of functional platelets observed in vivo; and (4) to evaluate clinical potential of snaclecs in preventing arterial thrombosis in a mouse model. To efficiently reach our goals the project’s implementation work plan is divided into 6 workpackages (WPs). Besides WP1, which is aimed at stimulating a strong and efficient interaction amongst WPs and all five partner groups, and WP6, which is devoted to dissemination of our achievements, the experimental part of the work is concentrated in WP2 to WP5, each relating to one of the above stated four main project goals. The two main deliverables of the proposed project are: (1) a thorough characterization of the Vaa venom component(s) responsible for inducing profound and transient thrombocytopenia in patients and (2) a description of the mechanism of its action on the molecular level. Both results are essential for the further development of a novel group of antiplatelet agents. According to the ample experience and high competence of all partners, availability of all research equipment necessary to conduct the planned experiments, numerous international collaborations, and a track of very successful collaborations of the implicated research groups in the past, we are certain that the goals are realistically set and achievable within the three-year period.