© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS
aDepartment of Medicine II, Medical University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
bDepartment of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany
cDepartment of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560, Japan
hheine{at}fz-borstel.de
* Corresponding author. Tel.: +49-4537-188420; fax: +49-4537-188697
Objective: Blood levels of cytokines are commonly elevated in severe congestive heart failure (CHF) and in coronary artery disease (CAD). While the adverse effects of cytokines on contractile function and myocardial cell integrity are well studied, little is known on whether cardiac cells are only targets or active players in these inflammatory reactions. Methods and results: We tested if human coronary artery endothelial cells (HCAEC) may become a source of cytokine and adhesion molecule expression when stimulated with bacterial lipopolysaccharide (LPS). Analysis of HCAEC supernatants by ELISA identified enhanced secretion of IL-6, IL-8, and MCP-1 while endothelin-1 was not increased. IL-1β, IL-10, or TNF-
were not detectable by ELISA while RT-PCR revealed enhanced mRNA expression of IL-1β and TNF- but not IL-10. FACS analysis showed an LPS-induced upregulation of ICAM-1, VCAM, and ELAM-1. LFA-1 could not be detected. We further characterized receptors involved in LPS-induced signaling. Our results indicate that activation of HCAEC by LPS requires Toll-like receptor (TLR) 4. Pretreating the cells with the 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitor Cerivastatin reduced IL-6 release. Conclusions: Taken together, our results indicate that activated HCAEC may act as inflammatory cells and thus directly contribute to the progression of CHF and CAD.
KEYWORDS Heart failure; Endotoxins; Infection/inflammation; Endothelial factors; Cytokines
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