Báo cáo y học: Fibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Fibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism...
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Báo cáo y học: " Fibrinogen decreases cardiomyocyte contractility through an ICAM-1-dependent mechanism" Available online http://ccforum.com/content/12/1/R2Research Open AccessVol 12 No 1Fibrinogen decreases cardiomyocyte contractility through anICAM-1-dependent mechanismJohn H Boyd, Edmond H Chau, Chiho Tokunanga, Ryon M Bateman, Greg Haljan, Ehsan Y Davani,Yinjin Wang and Keith R WalleyUniversity of British Columbia Critical Care Research Laboratories, St. Pauls Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, CanadaCorresponding author: John H Boyd, jboyd@mrl.ubc.caReceived: 18 Jul 2007 Revisions requested: 5 Sep 2007 Revisions received: 14 Oct 2007 Accepted: 3 Jan 2008 Published: 3 Jan 2008Critical Care 2008, 12:R2 (doi:10.1186/cc6213)This article is online at: http://ccforum.com/content/12/1/R2© 2008 Boyd et al.; licensee BioMed Central Ltd.This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractIntroduction Cardiomyocytes exposed to inflammatory microscopy with double-staining of isolated rat cardiomyocytesprocesses express intracellular adhesion molecule-1 (ICAM-1). demonstrated colocalization of ICAM-1 and fibrinogen. ThisWe investigated whether fibrinogen and fibrinogen degradation interaction was disrupted through pre-treatment of the cells withproducts, including D-dimer, could alter cardiomyocyte an ICAM-1-blocking antibody. Functionally, isolated ratcontractile function through interaction with ICAM-1 found on cardiomyocyte preparations exhibited decreased fractionalinflamed cardiomyocytes. shortening when incubated with fibrinogen, and through the use of synthetic peptides, we determined that residues 117–133 ofMethods In vivo, rats were injected with endotoxin to model the fibrinogen gamma chain are responsible for this interactionsystemic inflammation, whereas isolated rat cardiomyocytes with ICAM-1. Despite having crosslinked gamma chains, D-were treated with tumor necrosis factor-alpha to model the dimer retained the ability to decrease cardiomyocyteinflammatory environment seen following exposure to bacterial contractility.products such as lipopolysaccharide.Results In vivo, endotoxin administration profoundly decreased Conclusion Site 117–133 of the fibrinogen gamma chain iscardiac contractile function associated with a large increase in able to depress cardiomyocyte contractility through bindingintracardiac ICAM-1 and perivascular fibrinogen. Confocal ICAM-1.Introduction aling via the cytoskeleton [9]. While studies using cardiomyo-Both local and systemic inflammation impair cardiac contrac- cyte/leukocyte co-culturing methods demonstrate thattility, although the precise mechanism behind this is still activated leukocytes can bind to ICAM-1 with a resultantunclear [1-3]. It is now recognized that high levels of inflamma- decrease in myocardial contractility [9-11], we and otherstory biomarkers such as C-reactive protein and D-dimer are have noted a paucity of intramyocardial leukocytes in wholeassociated with an increased incidence of, and worse progno- animal models of inflammation [12,13]. Therefore, we postu-sis for, cardiovascular disease [4-8]. However, whether these lated that in the more complex environment of an in vivo model,molecules are simply markers of the inflammatory process or ICAM-1 ligands other than the CD11/CD18 receptors foundmight actually play a causative role in the resultant organ dys- on activated leukocytes [14-16] play a greater role in ICAM-1-function is not known. We previously reported a novel two- dependent decreases in cardiomyocyte contractility.step regulatory mechanism of cardiomyocyte contractilitywhereby systemic inflammation induces cardiomyocyte- Fibrinogen, a 340-kDa plasma glycoprotein with a physiologi-expressed intracellular adhesion molecule-1 (ICAM-1), whose cal plasma concentration of 1.5 to 4.5 g/L, as well as itssubsequent ligation results in decreased contractility by ...