Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany.
Eur J Heart Fail. 2011 Oct;13(10):1052-9. doi: 10.1093/eurjhf/hfr098. Epub 2011 Aug 4.
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.
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.
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.
自身免疫性心肌肌钙蛋白 I（cTnI）在缺血后早期对梗死心肌有有害影响。在这里，我们探讨了 cTnI 自身免疫在长期内的影响。此外，我们研究了 cTnI 自身免疫对再灌注损伤（IRI）后再血管化措施的梗死心肌的影响，这更接近临床实际情况。
用 cTnI（n=10）或对照缓冲液（n=14）免疫 A/J 小鼠，然后进行慢性冠状动脉结扎。另一组用 cTnI 免疫的小鼠（n=13）进行短暂的冠状动脉闭塞，并与未免疫的对照小鼠（n=17）进行比较。通过超声心动图评估左心室功能。获取心脏进行组织学评估。通过分析细胞因子和趋化因子模式以及抗 cTnI 抗体滴度来量化免疫反应。心肌炎症和心功能障碍可在心肌梗死（MI）后 180 天检测到。先前的 cTnI 免疫增强了心肌炎症和功能障碍。在 IRI 之前接受 cTnI 免疫的小鼠表现出更高的炎症评分、上调的促炎趋化因子（IP-10、MIP-1、Ltn、RANTES、TCA-3）和趋化因子受体（CCR2、CCR5）表达、增加白细胞介素（IL）-2、干扰素（IFN）-g，以及减少 IL-10 产生，与对照组相比，IRI 后分数缩短明显减少。
我们的结果首次表明，cTnI 诱导的自身免疫反应不仅导致慢性冠状动脉结扎后 180 天心肌炎症增加和心功能受损，而且与未免疫的对照组相比，还加剧了缺血/再灌注损伤。因此，cTnI 自身免疫的存在可能使患者更容易受到潜在的心肌损伤，无论是 MI 还是继发性再血管化措施。
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