Activation of Notch signaling in cardiomyocytes during post-infarction remodeling

作者:Oie Erik*; Sandberg Wiggo J; Ahmed Mohammad Shakil; Yndestad Arne; Laerum Ole Didrik; Attramadal Havard; Aukrust Pal; Eiken Hans Geir
来源:Scandinavian Cardiovascular Journal, 2010, 44(6): 359-366.
DOI:10.3109/14017431.2010.511256

摘要

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). Design. 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. Conclusion. The Notch signaling system is present in the cardiomyocytes and activated in HF, indicating a role of Notch signaling during myocardial remodeling in HF.

  • 出版日期2010-12