Protein clues to sudden cardiac death mysteries

Rebecca BurbidgeThursday, 26 February 2015

Scientists have uncovered critical new links between proteins and sudden cardiac death (SCD) as campaigners lobby for compulsory heart screening for young people.

Sudden cardiac death is an unexpected death caused by loss of heart function in a young person without a previously recognised cardiovascular issue. In the UK alone, twelve young people die each week from sudden cardiac death. The causes of SCD can be divided into three types: structural abnormalitie, electrical abnormalities and external causes.

Researchers at Oxford University have discovered that the protein iASPP has a surprising role in regulating the ‘glue’ that holds heart cells together, which may explain how a corresponding gene defect could cause SCD. Lead investigator Prof Xin Lu said: “We set out to investigate how this protein might cause cancer and found by chance that it could play a key role in this rare genetic heart condition”.

The researchers found that mice lacking a functional gene for the protein iASPP died prematurely of sudden cardiac death. Further investigation fo und that the iASPP protein controlled desmosomes – structures that act to ‘glue’ individual heart muscle cells together. A faulty iASPP gene was shown to affect the function of desmosomes, which the studies suggest can threaten the structural integrity of the heart and predispose humans and animals to arrhythmogenic right ventricular cardiomyopathy (ARVC), a leading cause of sudden cardiac death.

Going forward, the researchers highlight the need for further studies into iASPP to establish exactly how it controls desmosomal structure and function in order to maintain heart tissue integrity for proper mechanical and electrical activity. Follow up research will look into families with ARVC to see if testing the iASPP gene could help identify those at risk. The ultimate aim is the development of a reliable biomarker which could help clinicians to manage and advise people to make lifestyle choices to reduce their risk of sudden cardiac death.

Meanwhile, researchers from University of Vermont’s Cardiovascular Research Institute have discovered that the position of Myosin-binding protein C (cMyBP-C) in the muscle cells of the heart is critical to keeping the heart beating in rhythm. A small divergence from the metronomic rhythm of the heart can cause arrhythmias which can lead to sudden cardiac death in healthy young adults.

Using an animal model of a healthy heart, the researchers studied the physiology of sarcomeres – the fibrous proteins that make up the heart muscle cells. They found that cMyBP-C enables the sarcomeres to contract synchronously to create regular beats.

The next step is to understand what goes wrong with cMyBP-C in a diseased heart. In the future the researchers believe the protein could be a drug target for arrhythmias. Dr Dean E. Albert Reece said: “This work by Dr Lederer and his colleagues is a great example of collaborative basic science research with potentially huge translational implications”.