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Redefining protein function in thrombosis

Centenary Institute & University of Sydney

Grant:
  • Cardiovascular Senior Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Professor Phillip Hogg

Project summary

Implications for pro-thrombotic states and anti-thrombotic drug resistance in patients with cardiovascular disease.

What is the issue for NSW?

Proteins are responsible for all of life’s processes and are the most sophisticated molecules made in nature. Professor Phillip Hogg’s research has changed our concept of how proteins work, discovering that several proteins involved in cardiovascular disease exist and function not as a single form but as a multitude of different forms.

This has significant implications for how these proteins function generally and for drug resistance and drug development in cardiovascular disease. For example, if a drug binds preferentially to one or more forms of a protein, then events that reduce the incidence of these forms in individuals would result in drug resistance. Similarly, if drugs are developed against some forms of a protein but not others, this will inevitably result in drug resistance in some individuals. This project will focus on the importance of this discovery for the formation of blood clots.

Blood clots in heart blood vessels both accelerate the development of heart disease as well as trigger heart attacks. Many individuals have a heightened tendency to form blood clots for usually unknown reasons, so it has been difficult to reduce their lifetime risk of cardiovascular disease. In addition, preventing clots forming in diseased heart blood vessels and on implanted blood vessel stents is an ongoing challenge, as the current anti-clotting drugs are ineffective in up to half of patients for often unknown reasons.

The discovery that proteins involved in blood clotting exist in many different forms represents an entirely novel aspect of how and why blood clots form. This finding may underlie why some individuals have increased tendency to form blood clots and why they are often resistant to anti-clotting drugs.

What does the research aim to do and how?

Professor Hogg will investigate these questions in patients with coronary artery disease, heart failure and type II diabetes. These three cardiovascular diseases are strongly associated with blood clot formation. A better understanding of why blood clots form and why patients can be resistant to anti-clotting drugs will enable personalised anti-clotting therapy and development of more effective anti-clotting drugs. The long-term aim is to develop new anti-clotting drugs that overcome the resistance to the current drugs.