Projects / Programmes
Microvesicles as risk factors for secondary thromboembolic events
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B007 |
Biomedical sciences |
Medicine (human and vertebrates) |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Microvesicles, cell membranes, thromboembolisms, cancer, autoimmune diseases
Researchers (16)
Organisations (6)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0104 |
National Institute of Chemistry |
Ljubljana |
5051592000 |
21,377 |
| 2. |
0312 |
University Medical Centre Ljubljana |
Ljubljana |
5057272000 |
75,631 |
| 3. |
0381 |
University of Ljubljana, Faculty of Medicine |
Ljubljana |
1627066 |
45,408 |
| 4. |
0382 |
University of Ljubljana, Faculty of Health Sciences |
LJUBLJANA |
1627155 |
14,152 |
| 5. |
0481 |
University of Ljubljana, Biotechnical Faculty |
Ljubljana |
1626914 |
65,921 |
| 6. |
1538 |
University of Ljubljana, Faculty of Electrical Engineering |
Ljubljana |
1626965 |
27,615 |
Abstract
Microvesicles are created in the budding process and reflect the composition of the mother cell. They convey matter and information between cells and take part in spreading of inflammation, infection and cancer as well as in thromboembolic disorders secondary to these conditions. Controlled manipulation of the budding process presents a possible mechanism of slowing down the development of some diseases and of decreasing the risk for thromboembolic events while assessment of MVs is a possible method for determination of the risk for thromboembolisms. Understanding of the budding and vesiculation process in vivo and during isolation is yet rudimentary while the existing methods of quantitative assessment of MVs are poorly repeatable and inaccurate and are not yet suitable for use in clinical practice. Preliminary results indicate that a breakthrough to clinically relevant methods is possible only by technological advancement in equipment and a systematic approach to interpretation of clinical studies on large and diverse populations of patients. The scope of the project is improvement of the understanding and assessment of microvesiculation, to render it applicable in clinical practice.
Aims
Improvement of the understanding of membrane budding and vesiculation processes and connection of these mechanisms to thromboembolisms
Improvement and standardisation of methods for isolation and assessment of MVs
Determination of parameters of microvesiculation which are connected to the risk for thromboembolisms, in particular, secondary to cancer and autoimmune diseases, due to side effects of drugs and due to therapeutic procedures
Development of simple, low cost, life friendly, clinically relevant diagnostic methods based on characterization of MVs from blood
Characterization of substances that would by suppression of microvesiculation act as anticoagulants
Expected results
Elucidation of the origin of MVs in blood isolates, improvement of methods for determination of concentration of MVs in isolates, improvement of methods for MV characterization, reflecting an increased risk for thromboembolisms, and determination of natural anticoagulants acting as suppressors of microvesiculation.
Methods
Budding and microvesrovesiculation will be considered theoretically and experimentally in artificial membranes and in body fluid samples. In mathematical models we will take into account curvature sorting of membrane constituents and cell deformation due to centrifugation and shear forces in the fluid. Mechanisms of membrane budding will be studied in artificial membranes (phospholipid vesicles) which will be acquired by electroformation. MV will be isolated from body fluids by centrifugation and washing and observed by optical methods and by different microscopic techniques. Proteomic analysis and analysis of the nucleic acid content of MVs will be performed. Quantitative assessment of MVs isolated from blood will be interpreted in the view of clinical status of patients with increased risk for thromboembolisms and of healthy volunteers.
Relevance and potential impact of results
Improvement of methods for assessment of risk for thromboembolic events and the corresponding methods for their prevention will have positive medical, ethical, social and economic consequences. Thromboembolisms can cause death or debilitation, decrease the quality of life of patients and their relatives and present economic burden to society. Determination of substances that suppress microvesiculation and thereby act as anticoagulants will have an impact also on methods for slowing down the spreading of cancer. The proposed project would enable exploitation of the project IMIPEB within the initiative EUREKA, for which Slovenian partners were conditionally granted by MVZT (the number of the document 430-124/2009/333 from 22.10.2010). The worth of the entire project is around 1M EUR with Slovenian share 450.000 EUR. The coordinator of the project IMIP
Significance for science
In theoretical field, the results contribute to elucidation of interactions in complex systems- In experimental field, the results contribute to elucidation of mechanisms of intercellular communication which are fundamental for functioning of living organisms. In clinical field, the results contribute to implementation of understanding of the above basic processes in diagnostic and therapeutic procedures. The results promote biophysics as a clinically relevant description of the system on the basis of biophysical mechanisms.
Significance for the country
Within the project we collaborated with experts home and abroad and in this way broadend our knowledge. Of particular importance is the fact that, in collaboration with top experts, young associates were able to develop their knowledge. We included into the process of scientific work also undergraduate and graduate students. Three PhD theses were defended and one is in the final stage, of which there are two from the field of medicine and two from the field of nanosciences. Eva Ogorevc continues her work in a renowned research group in Lausanne, Switzerland , Roman Štukelj and Rado Janša are employed in Slovenia. Our contribution has increased the reputation of participant institutions and society in the international scientific and professional community. Particular attention was paid to the ethical aspects of research. We did not perform any experiments that would burden the patients and require life or suffering of animals, nor have we used chemicals obtained by such means. We have strived for development of methods where theoretical biophysics would bear the load and not a repetition of a large number of experiments that cause suffering. In this way we have contributed to raising the quality of life of individuals and society.
Most important scientific results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
