Andrié R, Braun P, Heinrich K-W, Lüderitz B, Bauriedel G
Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany,
Z Kardiol. 2003 Aug;92(8):641-9. doi: 10.1007/s00392-003-0951-2.
Increasing evidence supports a link between serological evidence of prior exposure to infectious pathogens, pathogen burden, and the risk for future myocardial infarction and death in patients with coronary artery disease. Based on this concept, we evaluated the intimal presence of four pathogens in human coronary atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect of pathogen burden on the expression of human heatshock protein 60 (hHSP60), a key protein in (auto-)immune pathogenesis of atherosclerosis. Coronary atherectomy specimens retrieved from 53 primary target lesions of patients with ACS (n=33) or SA (n=20) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (C. pn.), Helicobacter pylori (H.p.), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV), and for the expression of hHSP60. Chlamydia pneumoniae was present in 74%, Helicobacter pylori in 32%, CMV in 13% and EBV in 42%. Exclusively C.pn. revealed a prevalence in ACS (91%) vs SA (45%; p<0.001). Immunohistochemical analysis revealed 6 lesions without, 21 lesions with 1, 17 lesions with 2, 6 lesions with 3 and 3 lesions with 4 infectious agents. As an important finding, the mean value in ACS lesions was significantly increased compared to those in SA (1.9 vs 1.1; p<0.01). ACS-subgroup analysis revealed the highest mean value in patients with pain at rest within the last two days (Braunwald class III). In addition, expression of hHSP60 was significantly higher in ACS (8.7%) compared to SA (1.3%; p<0.001). Pathogen burden correlated highly significant (p<0.01) with the expression of hHSP60 (r=0.44).Our data demonstrate the impact of intimal pathogen burden in plaque instability, and suggest the presence of (auto-)immunoreactions against upregulated hHSP60 as an important pathomechanism that may contribute to acute coronary syndromes.
越来越多的证据支持既往接触感染性病原体的血清学证据、病原体负荷与冠心病患者未来发生心肌梗死及死亡风险之间存在联系。基于这一概念，我们评估了人类冠状动脉粥样硬化斑块中四种病原体的内膜存在情况，这些病原体与急性冠状动脉综合征（ACS）和稳定型心绞痛（SA）临床上相关，以及病原体负荷对人类热休克蛋白60（hHSP60）表达的影响，hHSP60是动脉粥样硬化（自身）免疫发病机制中的一种关键蛋白。从53例ACS患者（n = 33）或SA患者（n = 20）的主要靶病变中获取的冠状动脉斑块切除术标本，通过免疫组织化学方法评估肺炎衣原体（C. pn.）、幽门螺杆菌（H.p.）、巨细胞病毒（CMV）和爱泼斯坦 - 巴尔病毒（EBV）的存在情况以及hHSP60的表达。肺炎衣原体的存在率为74%，幽门螺杆菌为32%，CMV为13%，EBV为42%。仅肺炎衣原体在ACS中的患病率（91%）高于SA（45%；p < 0.001）。免疫组织化学分析显示，6个病变无感染病原体，21个病变有1种，17个病变有2种，6个病变有3种，3个病变有4种感染病原体。一项重要发现是，ACS病变中的平均值与SA病变相比显著升高（1.9对1.1；p < 0.01）。ACS亚组分析显示，在过去两天内有静息痛的患者（Braunwald III级）中平均值最高。此外，ACS中hHSP60的表达（8.7%）显著高于SA（1.3%；p < 0.001）。病原体负荷与hHSP60的表达高度相关（p < 0.01）（r = 0.44）。我们的数据证明了内膜病原体负荷对斑块不稳定性的影响，并表明针对上调的hHSP60的（自身）免疫反应的存在是可能导致急性冠状动脉综合征的重要病理机制。
