title: Autoimmunity against cardiac troponin I in ischaemia reperfusion injury.
abstract: OBJECTIVE
  Autoimmunity against cardiac troponin I (cTnI) has deleterious effects on the infarcted myocardium early after onset of ischaemia. Here, we explored the impact of cTnI-autoimmunity in the long term. Furthermore, we studied the effects of cTnI-autoimmunity on the infarcted myocardium following revascularization measures in terms of ischaemia reperfusion injury (IRI), which resembles clinical reality more closely.
  
  
  RESULTS
  After immunization with either cTnI (n= 10) or a control buffer (n= 14), A/J mice underwent chronic coronary artery ligation. Another group of mice immunized with cTnI (n= 13) underwent temporary coronary artery occlusion and were compared with non-immunized controls (n= 17). Left ventricular function was evaluated by echocardiography. Hearts were obtained for histological evaluation. Immunological responses were quantified by analysis of cytokine and chemokine patterns as well as anti-cTnI antibody titres. Myocardial inflammation and cardiac dysfunction were detectable as late as 180 days after myocardial infarction (MI). Previous cTnI-immunization enhanced myocardial inflammation and dysfunction. Mice subjected to cTnI-immunization before IRI exhibited a higher inflammation score, an upregulated expression of pro-inflammatory chemokines (IP-10, MIP-1, Ltn, RANTES, TCA-3) and chemokine receptors (CCR2, CCR5), increased interleukin (IL)-2, interferon (IFN)-g, and decreased IL-10 production along with a markedly reduced fractional shortening after IRI compared with the controls.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that cTnI-induced autoimmune response not only leads to increased myocardial inflammation and impaired cardiac function 180 days after chronic coronary artery ligation, but also exacerbates ischaemia/reperfusion injury compared with non-immunized controls. Hence, the presence of cTnI-autoimmunity could render subjects more vulnerable to prospective myocardial injury, be it MI, or secondary revascularization measures.
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany.
authors.forename: H Christian
authors.initials: HC
authors.lastname: Volz
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Buss
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Stefan
authors.initials: S
authors.lastname: Göser
authors.forename: Martin
authors.initials: M
authors.lastname: Andrassy
authors.forename: Renate
authors.initials: R
authors.lastname: Ottl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Ziya
authors.initials: Z
authors.lastname: Kaya
mesh_terms: D000818:Animals; D015551:Autoimmunity; D017931:DNA Primers; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D009203:Myocardial Infarction / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000276:immunology*; D019210:Troponin I / Q000276:immunology*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D019210:Troponin I