Activation of Notch signaling in cardiomyocytes during post-infarction remodeling.
OBJECTIVE
Notch signaling is crucial for cell-to-cell interaction during cardiovascular development and may influence differentiation, proliferation, and apoptotic events. We investigated whether Notch signaling is activated during myocardial remodeling in heart failure (HF).


METHODS
Myocardial gene expression and localization of Notch receptors (Notch1-4) and ligands (Jagged1-2, and Delta-like (Dll)-1 and 4) were investigated in rats with HF after induction of myocardial infarction and in humans with HF.


RESULTS
All Notch receptors and ligands investigated and Notch intracellular domain (NICD) were present in rat and human myocardial tissue and in cardiomyocytes with differences in their relative expression levels and altered expression levels in failing vs. non-failing myocardium. In isolated rat cardiomyocytes, Notch3 and Notch4 appeared to be the major Notch receptors, and Notch3 and Notch4 mRNA levels and NICD-3 and -4 in cardiomyocytes were upregulated in chronic HF (p < 0.05), indicating increased Notch3 and Notch4 signaling.


CONCLUSIONS
The Notch signaling system is present in the cardiomyocytes and activated in HF, indicating a role of Notch signaling during myocardial remodeling in HF.
Øie
Erik
E
Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. erik.oie@medisin.uio.no
Sandberg
Wiggo J
WJ
Ahmed
Mohammad Shakil
MS
Yndestad
Arne
A
Lærum
Ole Didrik
OD
Attramadal
Håvard
H
Aukrust
Pål
P
Eiken
Hans Geir
HG
D000818:Animals; D015153:Blotting, Western; D018450:Disease Progression; D006333:Heart Failure / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013599:Systole; D013997:Time Factors
D008024:Ligands; D012333:RNA, Messenger; D051880:Receptors, Notch