Cardiomyocyte progerin confers hypertrophy

Hutchinson-Gilford progeria syndrome (HGPS) is a rapidly progressive aging disease caused by a point mutation in lamin A (LMNA, c.1824C>T), leading to alternate splicing of the gene. Progerin—the truncated protein product—functions as a dominant negative and disrupts the nuclear envelope, alters chromatin architecture, and promotes DNA damage. Recently, a longitudinal echocardiographic study identified a subset of children with HGPS develop cardiac hypertrophy and diastolic dysfunction. This pathology is unique to HGPS, as other LMNA mutations cause dilated cardiomyopathy in humans. We observed cardiac hypertropy in transgenic mice over a period of 6 months. We then developed cardiomyocyte-restricted progerin expression and observed significant hypertrophy and diastolic dysfunction over 9 months.