Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.
Proc Natl Acad Sci U S A
; 105(6): 2111-6, 2008 Feb 12.
Article
in En
| MEDLINE
| ID: mdl-18256189
ABSTRACT
Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiomyopathy, Dilated
/
Ribonuclease III
/
Heart Failure
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2008
Document type:
Article
Affiliation country:
United States