Campean Valentina, Neureiter Daniel, Nonnast-Daniel Barbara, Garlichs Christoph, Gross Marie-Luise, Amann Kerstin
Department of Pathology, University of Erlangen-Nürnberg, Germany.
Atherosclerosis. 2007 Jan;190(1):156-66. doi: 10.1016/j.atherosclerosis.2006.01.014. Epub 2006 Feb 21.
The high incidence of cardiovascular complications in patients with chronic renal failure (CRF) is partly explained by more aggressive atherosclerosis, i.e. increased incidence and severity of lesions with higher tendency to calcification. The pathogenesis of this accelerated atherosclerosis, however, is not completely understood. Among other risk factors, chronic micro-inflammation may be involved. Activation of cells and adhesion molecules in atherosclerosis is governed by CD40-CD154 (CD40 ligand) interaction. Therefore, we investigated the expression and distribution of CD40-CD154 in different coronary atherosclerotic lesions of CRF patients and non-renal control patients. Coronary plaques of 57 patients with and without CRF were categorized according to the Stary classification and analysed for in situ protein expression of CD40, CD154 and CRP using immunohistochemistry and a semiquantitative scoring system. The nature, number and distribution of infiltrating cells was analysed and correlated to the types of coronary lesions and in particular to the presence of calcification. CD40 was over expressed in media myocytes of coronary plaques of both uremic and control patients. Inside the plaques, CD40 was expressed on endothelial cells, T lymphocytes, macrophages, fibroblasts, and smooth muscle cells. CD154 expression was seen on T cells in areas densely infiltrated by CD40 positive macrophages. In uremic and control patients higher in situ expression of CD40, CD154 and CRP was seen in calcified compared to non-calcified lesions. Inside the plaques, there were significant differences in the expression pattern of CD40 and CD154 between uremic and control patients. In addition, in uremic patients coronary plaques showed higher CRP protein expression compared to control patients. The data indicate a higher inflammatory status of coronary lesions as well as involvement of the CD40-CD154 signaling cascade in CRF patients, especially in cases of calcified atherosclerotic lesions.
慢性肾衰竭（CRF）患者心血管并发症的高发生率部分原因是动脉粥样硬化更严重，即病变的发生率和严重程度增加，钙化倾向更高。然而，这种加速动脉粥样硬化的发病机制尚未完全明确。在其他危险因素中，慢性微炎症可能参与其中。动脉粥样硬化中细胞和黏附分子的激活受CD40 - CD154（CD40配体）相互作用的调控。因此，我们研究了CRF患者和非肾性对照患者不同冠状动脉粥样硬化病变中CD40 - CD154的表达和分布。对57例有或无CRF患者的冠状动脉斑块按照Stary分类进行归类，并使用免疫组织化学和半定量评分系统分析CD40、CD154和CRP的原位蛋白表达。分析浸润细胞的性质、数量和分布，并将其与冠状动脉病变类型，特别是钙化的存在情况相关联。CD40在尿毒症患者和对照患者冠状动脉斑块的中层心肌细胞中均过度表达。在斑块内部，CD40在内皮细胞、T淋巴细胞、巨噬细胞、成纤维细胞和平滑肌细胞上表达。在CD40阳性巨噬细胞密集浸润的区域，T细胞上可见CD154表达。与未钙化病变相比，尿毒症患者和对照患者钙化病变中CD40、CD154和CRP的原位表达更高。在斑块内部，尿毒症患者和对照患者CD40和CD154的表达模式存在显著差异。此外，与对照患者相比，尿毒症患者冠状动脉斑块显示出更高的CRP蛋白表达。数据表明CRF患者冠状动脉病变的炎症状态更高，且CD40 - CD154信号级联参与其中，尤其是在钙化动脉粥样硬化病变的情况下。
