Noutsias M, Seeberg B, Schultheiss H P, Kühl U
Department of Cardiology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany. noutsias@zedat,fu-berlin.de
Circulation. 1999 Apr 27;99(16):2124-31. doi: 10.1161/01.cir.99.16.2124.
Dilated cardiomyopathy (DCM) is pathogenically linked to inflammatory cardiomyopathy (InfCM), which is characterized by intramyocardial infiltration. The transendothelial migration of immunocompetent cells is mediated by cell adhesion molecules (CAMs).
We investigated the expression pattern of CAMs (immunoglobulin superfamily, 32 selectins, and beta1- and beta2-integrins) in endomyocardial biopsies from DCM patients (n=152; left ventricular ejection fraction <40%) using immunohistochemistry. Whereas few specimens obtained at autopsy (controls; n=14) presented enhanced expression regarding single endothelial CAMs (human leukocyte antigen [HLA] class I, 7%; HLA-DR, 14%; CD29, 14%), none demonstrated concurrent abundance of >3 CAMs (inflammatory endothelial activation), nor did any control tissue prove positive for InfCM (>7.0 CD3+ lymphocytes per 1 mm2). In comparison, 64% (n=97) of the DCM biopsies were evaluated positive for InfCM and 67% (n=101) for inflammatory endothelial activation, respectively. Whereas expression of HLA class I, HLA-DR, intercellular cell adhesion molecule-1, and CD29 was distributed homogeneously within a patient's serial sections, immunoreactivity of vascular cell adhesion molecule-1, lymphocyte function antigen-3, and the selectins was accentuated on single vascular endothelia. Sixty-six percent of the DCM biopsies presented CD29 abundance also within the extracellular matrix and the sarcolemma. CD62P and CD62E were present in 16% and 40% of the DCM patients, respectively. Endothelial CAM representatives correlated with one another (P<0.05), except for CD62P with HLA. Endothelial CAM expression correlated with intramyocardial infiltrates phenotyped by the corresponding counterreceptors.
Inflammatory endothelial activation is present in 67% of DCM patients. Because CAM expression correlates with the immunohistological diagnosis of InfCM and counterreceptor-bearing intramyocardial infiltrates, evaluation of endothelial CAMs might be of diagnostic significance in InfCM.
扩张型心肌病（DCM）在发病机制上与炎症性心肌病（InfCM）相关，后者以心肌内浸润为特征。免疫活性细胞的跨内皮迁移由细胞黏附分子（CAMs）介导。
我们采用免疫组织化学方法研究了DCM患者（n = 152；左心室射血分数<40%）心内膜活检组织中CAMs（免疫球蛋白超家族、32种选择素以及β1和β2整合素）的表达模式。而在尸检获取的少量标本（对照组；n = 14）中，仅有少数标本单个内皮CAMs表达增强（人类白细胞抗原[HLA]I类，7%；HLA-DR，14%；CD29，14%），没有标本显示同时有>3种CAMs表达丰富（炎症性内皮激活），也没有任何对照组织InfCM检测呈阳性（每1平方毫米>7.0个CD3 +淋巴细胞）。相比之下，分别有64%（n = 97）的DCM活检组织InfCM检测呈阳性，67%（n = 101）有炎症性内皮激活。虽然HLA I类、HLA-DR、细胞间黏附分子-1和CD29的表达在患者的连续切片中分布均匀，但血管细胞黏附分子-1、淋巴细胞功能抗原-3和选择素的免疫反应性在单个血管内皮上更为突出。66%的DCM活检组织在细胞外基质和肌膜中也有CD29表达丰富。CD62P和CD62E分别在16%和40% 的DCM患者中出现。内皮CAM代表之间相互关联（P<0 .05），CD62P与HLA除外。内皮CAM表达与通过相应反受体表型分析的心肌内浸润相关。
67%的DCM患者存在炎症性内皮激活。由于CAM表达与InfCM的免疫组织学诊断以及带有反受体的心肌内浸润相关，因此评估内皮CAMs可能对InfCM具有诊断意义。
