Understanding mechanical, electrical and chemical mechanisms of actin mutations causing human hypertrophic cardiomyopathy and impact of novel therapy

Hypertrophic cardiomyopathy (HCM) is an inherited condition with a 50% chance of inheritance (autosomal dominant inheritance).

It results in the heart muscle becoming abnormally thickened and stiff which can cause problems with how the heart pumps blood around your body. Most people will have no symptoms, but some will have shortness of breath, chest pain, palpitation and/or blackouts.

The thickened area of the heart can also cause scarring and this scarring can cause problems with the heart rhythm disturbances which you result in palpitation.

In a small number of cases some abnormal heart rhythms can be fatal and often this is how we are alerted to this condition in the first place. Screening of family members can help determine whether someone is at risk of developing this condition.

Abnormalities in certain genes coding for heart muscle can lead to HCM and ewe plan to study known gene mutations of the actin protein of the heart muscle. We want to induce these changes in a yeast model to start with and transfer this to a zebrafish model.

This would allow us to study the beating function of the Zebrafish heart, blood flow patterns, measure its electrical activity, and assess the response to potentially novel drug treatments. Through this project we hope to try and use this to better understand HCM and develop new treatments for HCM patients.