A new study by the University of Oxford’s researchers has found a drug that may help repair heart function in diabetics who have heart attacks.
According to the study sponsored by the British Heart Foundation and published in the journal Diabetes, the drug, which is now in clinical trials as a potential therapy for a kind of anaemia, could help diabetic hearts heal and reduce their chance of developing heart failure.
During a heart attack, the heart’s blood flow is decreased or cut off, depriving the heart of oxygen (hypoxia). Diabetes causes cardiac cells to be less tolerant of hypoxia and, as a result, to die more quickly.
Now, the research team from Oxford has identified a drug known as molidustat that can improve levels of a protein that helps cells to adapt and survive when they are depleted of oxygen. They believe that providing molidustat to diabetics can aid in the recovery of their hearts after a heart attack and lower their risk of future issues, such as heart failure.
Molidustat, an orally administered drug, is now in phase III clinical studies for the treatment of anaemia in chronic renal disease. It acts by increasing the concentration of a protein known as Hypoxia-Inducible Factor 1 (HIF). When oxygen levels drop, HIF levels rise, prompting it to activate its ‘target’ genes, which aid in cell adaptation and survival. Previous research, however, has discovered that persons with diabetes had reduced levels of HIF in their heart cells.
When the researchers subjected human heart cells with insulin resistance, a type 2 diabetes symptom, to low levels of oxygen, they discovered that the increase in HIF protein levels was substantially lower than in control cells without insulin resistance. However, when the insulin resistance cells were treated with molidustat, the researchers observed higher levels of the HIF protein as well as activation of its target genes.
The researchers then evaluated the effect of molidustat on cardiac function by subjecting hearts from rats with and without type 2 diabetes to low oxygen levels. After a time of low oxygen, the function of diabetic hearts was dramatically reduced. However, when these hearts were treated with molidustat, their function returned to that of those who did not have diabetes.
HIF is also involved in post-heart-attack repair processes, such as the formation of new blood vessels, a process known as angiogenesis. New blood arteries form to bypass the dead tissue and ensure a good blood supply to the heart’s surrounding parts that have survived.
Diabetic hearts have reduced angiogenesis, which is thought to be a vital step in the development of heart failure. Molidustat treatment of rats with type 2 diabetes resulted in increased levels of the signals involved in the formation of new blood vessels, according to the researchers. They anticipate that molidustat therapy will aid in improving blood supply to the heart following a heart attack in diabetics.
Dr Lisa Heather, BHF Intermediate Research Fellow at the University of Oxford, said:
“Even with optimal management, people with type 2 diabetes still have a higher risk of developing heart and circulatory diseases. They’re then more likely than people without diabetes to develop heart failure after a heart attack.
“Despite this, there are no treatments available to help the diabetic heart recover after a heart attack. We’re hopeful that we’ve identified a drug that can address this unmet need and improve outcomes for people with diabetes after a heart attack.”
Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said:
“Heart and circulatory diseases are the leading cause of death in people with diabetes, a condition which affects nearly 5 million people in the UK.
“These promising results suggest that drugs which stabilise HIF could become a new treatment to reduce the risk of heart failure after a heart attack in people with diabetes. Further research is now needed to translate these early stage findings into clinical benefit.”
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