Modulation of IL-33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers.

Journal Article

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. MATERIALS AND 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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Sánchez-Más, J; Lax, A; Asensio-López, MDC; Fernandez-Del Palacio, MJ; Caballero, L; Santarelli, G; Januzzi, JL; Pascual-Figal, DA

Published Date

  • July 2014

Published In

Volume / Issue

  • 44 / 7

Start / End Page

  • 643 - 651

PubMed ID

  • 24837094

Electronic International Standard Serial Number (EISSN)

  • 1365-2362

International Standard Serial Number (ISSN)

  • 0014-2972

Digital Object Identifier (DOI)

  • 10.1111/eci.12282

Language

  • eng