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Redox control of VWF processing and activity during thrombotic diseases

Heart Research Institute, Centenary Institute & University of Sydney

Grant:
  • Cardiovascular Early-Mid Career Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Dr. Paul Coleman

Project summary

Identifying novel proteins which can be targeted to stop blood clots from starting to develop.

What is the issue for NSW?

Cardiovascular (or circulatory) diseases comprise all diseases of the heart and blood vessels. Among these diseases, the four types responsible for the most deaths in NSW are: coronary heart disease, stroke, heart failure, and peripheral vascular disease. Circulatory diseases cause more than 15,000 deaths and 150,000 hospitalisations of NSW residents in
each year. Cardiovascular diseases accounted for 14% of the total disease burden in Australia in 2015, second only to cancers.

The cause of coronary heart disease and stroke is the formation of clots within the blood vessels. This process is called thrombosis. The thrombotic event causes impaired blood flow through the vessel and myocardial infarctions and strokes are the outcome.

What does the research aim to do and how?

Given the importance of preventing thrombosis and therefore diseases such as cardiovascular disease and stroke, Dr Coleman’s project aims to identify novel proteins which can be targeted to stop the clot from starting to develop.

To do this the project will study the Von Willebrand factor (VWF). In the circulation, VWF unfolds from an inactive conformation into an active string-like form that allows platelets and inflammatory cells such as neutrophils to anchor with blood vessels and a clot begins to develop.

Failure of the blood vessels to control the size and amount of VWF leads to increased amounts of long strands that promote excessive platelet adhesion and clot formation leading to thrombosis. There is increasing epidemiological and clinical evidence indicating that the incidence of thrombotic diseases, including heart attack and stroke, highly correlates with increased levels of vascular VWF and increased binding to platelets and neutrophils.

Dr Coleman’s study will be a collaboration between the Centenary Institute and Heart Research Institute. Utilising the resources of both Institutes, they hope to develop new ways to prevent cardiovascular diseases.