How do mutations affecting the nuclear envelope lead to dilated cardiomyopathy?

Understanding the role of the nuclear envelope in cardiovascular development and disease

Dilated cardiomyopathy (DCM) is one of the most common forms of inheritable heart disease. It affects the heart muscle, making it stretched and thin so that the heart can’t pump blood around the body efficiently. People with DCM are at risk of heart failure, and the only cure is a heart transplant. Better medicines are urgently needed to prevent or treat DCM, but progress is hampered by the fact that there is still so much we don’t know about how it develops. Some of the most common causes of inherited DCM are genetic mutations that affect a group of proteins surrounding the nucleus of the cell – called the nuclear envelope. In this study, Dr Stroud will examine the effects, in mice, of the mutations that affect one such protein, called Lem2. Little is known about Lem2’s role in the heart, or why faulty Lem2 could cause DCM. Dr Stroud plans to use a range of cutting-edge techniques to reveal more about how Lem2 works. The results of this work will improve our understanding of how changes in the proteins surrounding the nucleus affect the heart, and lead to DCM. The insights will expand our knowledge of DCM and may reveal targets for current or new medicines to improve the outlook for people living with the condition.