Fang Fang, Zhang Wei, Yang Li, Wang Zheng, Liu Dong-ge
Department of Pathology, Beijing Hospital, Beijing 100730, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Dec;39(12):1110-6.
To observe the expression of PECAM-1 and E-selectin in the vulnerable plagues and their relationships to myocardial Leu125Val polymorphism of PECAM-1 and Ser128Arg polymorphism of E-selectin in autopsied samples of patients with acute coronary syndrome (ACS).
We detected the expressions of PECAM-1 and E-selectin in the vulnerable plaques by immunohistochemistry on 50 autopsy samples of patients with ACS, 30 autopsy samples from non-cardiac disease patients served as control. Genetic Leu125Val polymorphism of PECAM-1 was detected by PCR-SSCP in myocardial paraffin blocks of 37 ACS cases and 43 control cases, and Ser128Arg polymorphism of E-selectin was detected by PCR-RFLP in myocardial paraffin blocks of 39 ACS cases and 43 control cases, respectively.
Immunohistochemical features: (1) the incidence of positive expression in the intima of coronary artery of PECAM-1 [76.0% (38/50) vs. 26.7% (8/30)] and E-selectin [26.0% (13/50) vs. 0] was significantly higher in ACS group than in control group (all P < 0.01). (2) Expressions of PECAM-1 [58.0% (29/50) vs. 28.0% (14/50)] and E-selectin [22.0% (11/50) vs.12.0% (6/50)] were significantly higher at neovascular endothelial cells in plaques than expressions at coronary arterial endothelial cells in ACS group (all P < 0.01). (3) In 41 plaques with inflammatory infiltration, the expression rates of PECAM-1 and E-selectin in inflammatory cell density of < 10, 10 - 30 and > 30/HPF were 33.3%, 68.2%, 92.3% and 16.7%, 31.8% and 23.1%, respectively. Genotype detection results: There is significant difference in frequencies of allele in Leu125Val polymorphism (P < 0.05), but the genotype distributional frequencies were similar (P > 0.05) between ACS group and control group. There are significant differences in frequencies of allele and genotype in Ser128Arg of E-selectin polymorphism between ACS group and control group (all P < 0.05).
The immunohistochemical expressions of PECAM-1 and E-selectin were significantly increased at intima in vulnerable plaques of ACS group, especially in neovascular endothelial cells, and positively correlated with inflammatory cell density, suggesting that PECAM-1 and E-selectin might play an important role in inflammatory reaction and development of vulnerable plaque. E-selectin Ser128Arg polymorphism is associated with ACS, and it might be a risk factor for ACS.
观察急性冠状动脉综合征(ACS)患者尸检样本中易损斑块内血小板内皮细胞黏附分子-1(PECAM-1)和E-选择素的表达情况,及其与PECAM-1基因Leu125Val多态性和E-选择素基因Ser128Arg多态性的关系。
采用免疫组织化学法检测50例ACS患者尸检样本中易损斑块内PECAM-1和E-选择素的表达,以30例非心脏疾病患者尸检样本作为对照。分别采用聚合酶链反应-单链构象多态性(PCR-SSCP)法检测37例ACS患者和43例对照者心肌石蜡块中PECAM-1基因Leu125Val多态性,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测39例ACS患者和43例对照者心肌石蜡块中E-选择素基因Ser128Arg多态性。
免疫组织化学特征:(1)ACS组冠状动脉内膜PECAM-1阳性表达率[76.0%(38/50)比26.7%(8/30)]和E-选择素阳性表达率[26.0%(13/50)比0]显著高于对照组(均P<0.01)。(2)ACS组斑块新生血管内皮细胞PECAM-1表达率[58.0%(29/50)比28.0%(14/50)]和E-选择素表达率[22.0%(11/50)比12.0%(6/50)]显著高于冠状动脉内皮细胞(均P<0.01)。(3)在41例有炎症浸润的斑块中,炎症细胞密度<10、10~30和>30/HPF时,PECAM-1表达率分别为33.3%、68.2%、92.3%,E-选择素表达率分别为16.7%、31.8%、23.1%。基因分型检测结果:ACS组与对照组PECAM-1基因Leu125Val多态性等位基因频率差异有统计学意义(P<0.05),但基因型分布频率相似(P>0.05)。ACS组与对照组E-选择素基因Ser128Arg多态性等位基因频率和基因型频率差异均有统计学意义(均P<0.05)。
ACS组易损斑块内膜PECAM-1和E-选择素免疫组织化学表达显著增加,尤其在新生血管内皮细胞,且与炎症细胞密度呈正相关,提示PECAM-1和E-选择素可能在易损斑块炎症反应及发展中起重要作用。E-选择素基因Ser128Arg多态性与ACS相关,可能是ACS的危险因素。