Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/30051
Conference/Presentation Title: | Pro-inflammatory action of MIF in acute myocardial infarction through activation of peripheral blood mononuclear cells. | Authors: | Morand E.F. ;Gao X.M.;Duffy S.J.;Dart A.M.;Du X.J.;White D.;Chan W.;Fang L.;Liu Y.;Taylor A.J. | Institution: | (White, Fang, Liu, Du, Gao) Baker IDI Heart and Diabetes Institute, Melbourne, Australia (Chan, Taylor, Duffy, Dart) Heart Centre, Alfred Hospital, Melbourne, Australia (Morand) Monash Medical Centre, Melbourne, Australia | Presentation/Conference Date: | 22-Sep-2011 | Copyright year: | 2011 | Publisher: | Oxford University Press | Publication information: | European Heart Journal. Conference: European Society of Cardiology, ESC Congress 2011. Paris France. Conference Publication: (var.pagings). 32 (SUPPL. 1) (pp 579), 2011. Date of Publication: August 2011. | Abstract: | Purpose: Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of many inflammatory disorders. We investigated whether MIF acts as both a biomarker of cardiac injury and mediator of inflammatory responses following acute myocardial infarction (AMI). Method(s): 42 AMI patients, 10 stable angina patients and 10 healthy volunteers were recruited. Blood samples were collected at hospital admission (average 3 h after onset of AMI) and peripheral blood mononuclear cells (PBMCs) separated and cultured. Levels of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin- 6 (IL-6) in both plasma and supernatant of cultured PBMC were measured by ELISA. Gene expression of these markers in PBMCs was determined by real-time PCR. PBMCs were cultured in control media or in the presence of COR100140 (an anti-MIF compound, 50 muM), neutralising anti-MIF antibody (10 ng/ml), IL-1beta (10 ng/ml), recombinant human MIF (rMIF, 5 ng/ml) or combination of IL-1beta and rMIF. AMI patients underwent cardiac magnetic resonance (CMR) examinations at day 3 and 3 months following AMI to measure left ventricular (LV) volumes, systolic function and infarct size. Result(s): Compared with controls, at day-1 post-AMI, plasma MIF levels were elevated by 2-3 fold and correlated positively with plasma levels of MMP-9 (r=0.64, P=0.01), IL-6 (r=0.70, P=0.004), peak troponin I (r=0.65, P<0.001) and creatine kinase (r=0.51, P<0.001). MIF plasma levels at day-1 post AMI also correlated positively with day-3 and 3 month CMR estimated infarct size (r=0.74, r=0.70, both P<0.001), LV end-diastolic (r=0.43, r=0.58, both P=0.005) and systolic volumes (r=0.63, r=0.60, both P<0.001), but negatively with LV ejection fraction (r=0.44, r=0.40, both P<0.02). Expression and production of MIF, MMP-9 and IL-6 by PBMCs were increased at day-3 (2-3 fold, P<0.05), but not at day-1 post-AMI. AMI or IL-1beta induced PBMC activation measured by up-regulation of MIF, MMP-9 and IL-6 (2-3 fold, P<0.05), which was attenuated by anti-MIF treatment. Further, IL-1beta-stimulated production of MMP-9 and IL-6 was significantly enhanced in the presence of exogenous rMIF by 35%. Conclusion(s): MIF is a key mediator of systemic and regional inflammation following AMI. Plasma MIF serves as a novel biomarker for myocardial inflammation and severity of tissue damage, and bears predictive values for acute and chronic dysfunction and remodelling post AMI. MIF inhibition attenuates PBMC activation induced by AMI or IL-1beta constituting a potential therapy to minimise inflammatory responses following AMI. | Conference Start Date: | 2011-08-27 | Conference End Date: | 2011-08-31 | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1093/eurheartj/ehr323 | ISSN: | 0195-668X | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/30051 | Type: | Conference Abstract | Subjects: | *society human plasma inflammation patient infarction blood level heart ejection fraction myocarditis predictive value therapy upregulation heart left ventricle volume cardiovascular magnetic resonance examination pathogenesis heart injury stable angina pectoris normal human blood sampling hospital admission supernatant gene expression real time polymerase chain reaction enzyme linked immunosorbent assay interleukin 6 interleukin 1 gelatinase B biological marker antibody troponin I creatine kinase factor A macrophage migration inhibition factor cytokine marker *peripheral blood mononuclear cell tissue injury *cardiology *acute heart infarction myocarditis tissue injury predictive value therapy upregulation heart left ventricle volume cardiovascular magnetic resonance examination pathogenesis heart injury stable angina pectoris normal human blood sampling hospital admission supernatant gene expression real time polymerase chain reaction enzyme linked immunosorbent assay infarction patient inflammation plasma human *peripheral blood mononuclear cell heart ejection fraction *society *acute heart infarction *cardiology blood level |
Appears in Collections: | Conferences |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.