Modulation of IL-33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers.
BACKGROUND
Interleukin (IL)-33 and sST2 are molecules with an opposite pathophysiologic implications in the myocardial response after acute myocardial infarction (AMI). Both may be a target for therapeutic interventions. The kinetics of IL-33 and sST2 expression in infarcted myocardium and their correlation with the ongoing processes of fibrosis, inflammation and apoptosis remains poorly defined.


METHODS
Fifty Wistar rats underwent left anterior descending coronary artery surgical ligation and were sacrificed at 1, 2, 4, 12 or 24 weeks post-AMI. A sham-operated group was also included. The mRNA cardiac expression levels of IL-33, sST2, fibrosis markers, inflammatory markers and apoptosis markers were assessed by RT-PCR. The protein expression of IL-33 was also measured by Western blotting.


RESULTS
The mRNA levels of IL-33 and sST2 were upregulated in the infarcted myocardium during the first week after AMI. However, while IL-33 levels remained elevated during the first 12 weeks post-AMI, sST2 levels showed a marked drop at 4 weeks. IL-33 protein expression showed a similar kinetic than mRNA expression. The expression of sST2 positively correlated with cardiac gene expression of inflammatory and fibrosis markers. However, the IL-33 level did not correlate with these cardiac remodelling markers. No correlation of sST2 with apoptosis markers was observed.


CONCLUSIONS
After AMI, expression of sST2 is rapidly upregulated during the first 4 weeks and, in contrast to IL-33, its levels correlated with the ongoing processes of fibrosis and inflammation. These findings suggest differential regulation of IL33 and sST2. Therapeutic modulation of early sST2 expression may be of greater importance to prevent adverse remodelling after AMI.
Cardiology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain; Department of Internal Medicine, School of Medicine, University of Murcia, Murcia, Spain.
Jesús
J
Sánchez-Más
Antonio
A
Lax
María Del Carmen
Mdel C
Asensio-López
Maria J
MJ
Fernandez-Del Palacio
Luis
L
Caballero
Giorgia
G
Santarelli
James L
JL
Januzzi
Domingo A
DA
Pascual-Figal
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D003331:Coronary Vessels / Q000601:surgery; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000502:physiology
D015415:Biomarkers; C553108:Il33 protein, rat; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; C000589812:ST2 protein, rat
Acute myocardial infarction; ST2; cardiac remodelling; interleukin