How a protein called prelamin A is involved in cardiomyopathy and ageing

Prelamin a accumulation causes nuclear lamina disruption and drives cardiomyocyte dysfunction in dilated cardiomyopathy

Professor Catherine Shanahan and her team at King’s College London are studying a protein called prelamin A. This toxic protein can accumulate in heart muscle cells causing them to function less efficiently, and this can lead to heart failure. Prelamin A is the inactive form of a protein called lamin A, that makes up the nuclear lamina, a meshwork that provides structural support for the nucleus, which is the part of the cell that houses its DNA. The nuclear lamina is emerging as an important factor for the cells of the heart to work well. Professor Shanahan has discovered prelamin A accumulates when dilated cardiomyopathy (DCM) develops (when the heart becomes enlarged and floppy) and also when the heart ages prematurely. In this project, Professor Shanahan and her team will study the role of the nuclear lamina in the progression of heart failure in DCM and in premature aging. They will investigate where prelamin A and the proteins it binds to are located within human heart cells, and study how prelamin A accumulation affects the adult mouse heart and cells from both humans and mice. This research will reveal how prelamin A accumulates in ageing and diseased hearts and how it contributes to heart failure during cardiomyopathy. It may identify new ways to treat cardiomyopathy and age-related heart failure.