Ott Stephan J, El Mokhtari Nour Eddine, Musfeldt Meike, Hellmig Stephan, Freitag Sandra, Rehman Ateequr, Kühbacher Tanja, Nikolaus S, Namsolleck Pawel, Blaut Michael, Hampe Jochen, Sahly Hany, Reinecke Alexander, Haake Nils, Günther Rainer, Krüger Dietmar, Lins Markus, Herrmann Gunhild, Fölsch Ulrich R, Simon Rüdiger, Schreiber Stefan
Institute for Clinical Molecular Biology, Department of General Internal Medicine, UKSH Campus Kiel, Kiel, Germany.
Circulation. 2006 Feb 21;113(7):929-37. doi: 10.1161/CIRCULATIONAHA.105.579979.
Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD.
We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33+/-3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients.
Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.
细菌感染被认为是冠心病（CHD）病理生理学中的一个潜在病因。本研究分析分子系统发育，以系统地探索冠心病患者动脉粥样硬化病变中细菌的存在、频率和多样性。
我们使用克隆文库、变性梯度凝胶分析和荧光原位杂交技术，研究了38例冠心病患者经导管定向旋切术获取的动脉粥样硬化组织、15例尸检患者的对照材料以及11例心脏跳动器官供体的对照材料中的16S rDNA特征。通过保守PCR在所有冠心病患者中均发现了细菌DNA，但在对照材料或任何正常/未受影响的冠状动脉中均未发现。荧光原位杂交证实了动脉粥样硬化病变中存在细菌。在一个合并文库的1500多个克隆中，证明了总体细菌多样性高，有超过50种不同的细菌，其中包括葡萄球菌属、普通变形杆菌、肺炎克雷伯菌和链球菌属，并通过变性梯度凝胶分析得到证实。动脉粥样硬化斑块中的平均细菌多样性较高，评分为12.33±3.81（范围为5至22）。一种特异性PCR在51.5%的冠心病患者中检测到衣原体属。
在所有冠心病标本中检测到多种分子特征表明，多样的细菌定植可能比单一病原体更重要。我们的观察结果不允许我们得出细菌是冠心病病因发病机制中的致病因素这一结论。然而，细菌病原体可能已继发定植于动脉粥样硬化病变，并可能作为加速疾病进展的一个额外因素。
