Fibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism.

TitleFibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism.
Publication TypeJournal Article
Year of Publication2008
AuthorsBoyd, JH, Chau, EH, Tokunanga, C, Bateman, RM, Haljan, G, Davani, EY, Wang, Y, Walley, KR
JournalCrit Care
Volume12
Issue1
PaginationR2
Date Published2008
ISSN1466-609X
KeywordsAnimals, Endotoxins, Fibrinogen, Inflammation, Intercellular Adhesion Molecule-1, Lipopolysaccharides, Male, Myocardial Contraction, Myocytes, Cardiac, Rats, Rats, Sprague-Dawley
Abstract

INTRODUCTION: Cardiomyocytes exposed to inflammatory processes express intracellular adhesion molecule-1 (ICAM-1). We investigated whether fibrinogen and fibrinogen degradation products, including D-dimer, could alter cardiomyocyte contractile function through interaction with ICAM-1 found on inflamed cardiomyocytes.METHODS: In vivo, rats were injected with endotoxin to model systemic inflammation, whereas isolated rat cardiomyocytes were treated with tumor necrosis factor-alpha to model the inflammatory environment seen following exposure to bacterial products such as lipopolysaccharide.RESULTS: In vivo, endotoxin administration profoundly decreased cardiac contractile function associated with a large increase in intracardiac ICAM-1 and perivascular fibrinogen. Confocal microscopy with double-staining of isolated rat cardiomyocytes demonstrated colocalization of ICAM-1 and fibrinogen. This interaction was disrupted through pre-treatment of the cells with an ICAM-1-blocking antibody. Functionally, isolated rat cardiomyocyte preparations exhibited decreased fractional shortening when incubated with fibrinogen, and through the use of synthetic peptides, we determined that residues 117-133 of the fibrinogen gamma chain are responsible for this interaction with ICAM-1. Despite having crosslinked gamma chains, D-dimer retained the ability to decrease cardiomyocyte contractility.CONCLUSION: Site 117-133 of the fibrinogen gamma chain is able to depress cardiomyocyte contractility through binding ICAM-1.

DOI10.1186/cc6213
Alternate JournalCrit Care
PubMed ID18173852
PubMed Central IDPMC2374637