BACKGROUND: Mutations in the LMNA gene are a common cause (6-8%) of dilated 
cardiomyopathy (DCM) leading to heart failure, a growing health care problem 
worldwide. The premature aging disease Hutchinson-Gilford syndrome (HGPS) is 
also caused by defined mutations in the LMNA gene resulting in activation of a 
cryptic splice donor site leading to a defective truncated prelamin A protein 
called progerin. Low levels of progerin are expressed in healthy individuals 
associated with ageing. Here, we aimed to address the role of progerin in 
dilated cardiomyopathy.
METHODS AND RESULTS: mRNA expression of progerin was analyzed in heart tissue of 
DCM (n = 15) and non-failing hearts (n = 10) as control and in blood samples 
from patients with DCM (n = 56) and healthy controls (n = 10). Sequencing 
confirmed the expression of progerin mRNA in the human heart. Progerin mRNA 
levels derived from DCM hearts were significantly upregulated compared to 
controls (1.27 ± 0.42 vs. 0.81 ± 0.24; p = 0.005). In contrast, progerin mRNA 
levels in whole blood cells were not significantly different in DCM patients 
compared to controls. Linear regression analyses revealed that progerin mRNA in 
the heart is significantly negatively correlated to ejection fraction (r = 
-0.567, p = 0.003) and positively correlated to left ventricular enddiastolic 
diameter (r = 0.551, p = 0.004) but not with age of the heart per se. Progerin 
mRNA levels were not influenced by inflammation in DCM hearts. 
Immunohistochemistry and Immunofluorescence analysis confirmed increased 
expression of progerin protein in cell nuclei of DCM hearts associated with 
increased TUNEL+ apoptotic cells.
CONCLUSION: Our data suggest that progerin is upregulated in human DCM hearts 
and strongly correlates with left ventricular remodeling. Progerin might be 
involved in progression of heart failure and myocardial aging.