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Targets for the prevention of cardiovascular thrombosis in metabolic syndrome

Heart Research Institute & University of Sydney

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

Project summary

Using new technology to measure effects of thiol enzymes, coupled with disturbed flow, and evaluation of a new blood test to detect sticky blood.

What is the issue for NSW?

Approximately one in five adult Australians have metabolic syndrome, a condition characterised by a combination of increased weight, high blood sugar, cholesterol and blood pressure in the same person that triples their risk of heart attack and stroke.

Heart attack and strokes result from the presence of “sticky” platelets that build up clots in the blood stream. Common drugs such as aspirin are not very effective in preventing “sticky” blood in metabolic syndrome; there is a pressing need to understand mechanisms causing this to develop new drugs to prevent clots.

What does the research aim to do and how?

The team discovered a group of enzymes in blood, named thiol isomerases, which control blood clot formation. These are overactive in metabolic syndrome, making platelets stickier.

Importantly, they found that these enzymes are particularly overactive under conditions of disturbed blood flow, as occurs when blood vessels are narrowed by cholesterol build up.

Using new technology, the team has developed a biochip to measure effects of thiol enzymes, coupled with disturbed flow, and are evaluating this as a new blood test to detect sticky blood. They envision that their flow chips will become a useful tool to detect prothrombotic tendency in patient samples and that inhibitors of thiol isomerases will prove to be an effective and safe treatment for individuals with metabolic syndrome.

With collaborators at Harvard University, the team identified a drug, isoquercetin, that inhibits thiol isomerase activity and can prevent vein clots in cancer patients. They will evaluate this in mice with metabolic syndrome to determine its ability to prevent thrombosis. If effective, they will perform a clinical study using isoquercetin treatment to decrease sticky blood in people with the metabolic syndrome.

Dr Freda Passam is a haematologist in the Royal Prince Alfred Hospital, Sydney, with a special interest in thrombosis and haemostasis. She leads the Haematology Research Group of the Heart Research Institute/University of Sydney in the Charles Perkins Centre focused on new mechanisms of clot formation that can lead to the development of efficient and safer antithrombotic drugs. She has a keen interest in the application of microfluidic devices for the detection of thrombotic tendency in patient samples.