Autoimmunity against cardiac troponin I in ischaemia reperfusion injury

• Verfasst von: Volz, Hans Christian [VerfasserIn]
• Verfasst von: Buß, Sebastian Johannes [VerfasserIn]
• Verfasst von: Li, Jin [VerfasserIn]
• Verfasst von: Göser, Stefan [VerfasserIn]
• Verfasst von: Andrassy, Martin [VerfasserIn]
• Verfasst von: Öttl, Renate [VerfasserIn]
• Verfasst von: Pfitzer, Gabriele [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Kaya, Ziya [VerfasserIn]
• Titel: Autoimmunity against cardiac troponin I in ischaemia reperfusion injury
• Verf.angabe: H. Christian Volz, Sebastian J. Buss, Jin Li, Stefan Göser, Martin Andrassy, Renate Öttl, Gabriele Pfitzer, Hugo A. Katus, and Ziya Kaya
• Jahr: 2011
• Umfang: 8 S.
• Fussnoten: Erstmals veröffentlicht: 18 February 2014 ; Gesehen am 27.10.2022
• Titel Quelle: Enthalten in: European journal of heart failure
• Ort Quelle: Oxford : Wiley, 1999
• Jahr Quelle: 2011
• Band/Heft Quelle: 13(2011), 10 vom: Okt., Seite 1052-1059
• ISSN Quelle: 1879-0844
• DOI: doi:10.1093/eurjhf/hfr098
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Autoimmunity
• Sach-SW: Cardiac troponin
• Sach-SW: Ischaemia
• Sach-SW: Myocardial infarction
• Sach-SW: Reperfusion injury
• K10plus-PPN: 1820181863

Abstract

Aims 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. Methods and 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. Conclusion 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.