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Why doesn’t HIF work in the heart?

Project summary

Hypoxia inducible factor (HIF) activation by sirtuins and hypoxia mimetics in the diabetic heart

In diabetes, researchers believe that lower levels of a protein called HIF make it harder for the heart cells to function during a heart attack. Dr Lisa Heather will investigate whether drugs which reactivate HIF can protect the heart.

Background to research

Heart failure is the most common cause of death in people with Type 2 diabetes. During a heart attack the supply of oxygen to the heart is restricted, resulting in damage to the heart cells. Normally, a protein called hypoxia-inducible factor (HIF) detects decreased oxygen levels and helps the heart cells to function without oxygen. In diabetes, however, researchers believe that lower levels of HIF in the heart limit this protective response.

Research aims

During her Diabetes UK RD Lawrence Fellowship, Dr Lisa Heather will investigate whether drugs that reactivate HIF can protect the heart and slow the development of heart failure. Dr Heather’s study aims to investigate whether HIF production is suppressed in the heart of people with diabetes, thereby increasing ischemic damage, (damage caused by the restriction of blood supply to tissues) impairing the heart’s ability to contract and effectively pump blood around the body. Dr Heather will also research whether HIF can be reactivated using a new drug treatment which could help protect the heart during times of reduced oxygen availability. The research will involve rats with Type 2 diabetes fed a high fat diet, which will be used to study the effect of HIF reactivation on heart function and structure using Magnetic Resonance Imaging (MRI). Dr Heather will also investigate whether reactivating HIF will increase glucose rather than fatty acid metabolism in the heart during times of reduced oxygen availability. Ischemic recovery and improvements in heart rate and contraction will also be studied. 

Potential benefit to people with diabetes

Dr Heather’s research could help to improve heart function and slow the progression of heart failure in people with diabetes. By reducing the use of fatty acid metabolism, which occurs due to the lack of oxygen, this could make the heart more resistant to energy starvation in ischemia and potentially help improve recovery following a heart attack in people with diabetes.

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