Fibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism
| Autor: | Greg Haljan, Ryon M. Bateman, John H. Boyd, Ehsan Y. Davani, Chiho Tokunanga, Yinjin Wang, Keith R. Walley, Edmond Chau |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Male Intercellular Adhesion Molecule-1 Inflammation 030204 cardiovascular system & hematology Fibrinogen Critical Care and Intensive Care Medicine Rats sprague dawley Contractility Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine medicine Animals Myocytes Cardiac 030304 developmental biology 0303 health sciences ICAM-1 business.industry Research Adhesion Myocardial Contraction 3. Good health Cell biology Rats Endotoxins Immunology medicine.symptom business Intracellular medicine.drug |
| Zdroj: | Critical Care |
| ISSN: | 1466-609X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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