Department of Cardiac Surgery, Ludwig Maximilians University Munich, Marchioninistr. 15, 81366, Munich, Germany.
Inflamm Res. 2011 May;60(5):439-45. doi: 10.1007/s00011-010-0282-5. Epub 2011 Feb 1.
Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and may lead to recurrent symptoms. Various data indicate that apoptosis is the main event occurring during development and progression of atherosclerotic plaque. Plaque vascular smooth muscle cells (VSMCs) are more sensitive than regular VSMCs to TP53-mediated apoptosis.
We investigated EDTA blood of 192 patients (18% female, age 60.9 ± 7.4 years) who had primary CABG more than 5 years ago. CAD progression was defined as clinical endpoints: re-operation (n = 88; 46%), catheter re-intervention (n = 58; 30%), or angina at follow-up (n = 89; 46%). Apoptotic gene polymorphisms (Toll-like receptor 2 A753G, FAS ligand C-844T, FAS promoter G-670A, TP53 Arg72Pro, and CD14 C-260T) were investigated by PCR-RFLP and compared to healthy controls (n = 200, 24% female, age 63.4 ± 5.4). Gender-specific analysis was carried out.
Heterozygous, homozygous and wild-type expression of all five genetic polymorphisms showed almost identical distribution between patients with CAD and healthy controls. Looking at clinical endpoints, with GG expression of Toll-like receptor 2 polymorphism and GG expression of FAS promoter polymorphism, results showed a relative increased risk (p = 0.09) for recurrent symptoms and re-intervention. Patients with FAS promoter polymorphism with AA expression had an increased risk of suffering from recurrent symptoms (n = 28, p = 0.04). We found that patients with homozygous expression of TP53 polymorphisms (n = 3, all male) were prone to needing re-intervention after prior CABG (p = 0.03), but not re-operation. Over a period up to 15 years, the re-intervention rate was significantly different in homozygous genotypes of FAS LG, FAS promoter and TP53.
Patients presenting with polymorphisms of FAS LG, FAS promoter and TP53 have an increased risk of CAD progression, as they have a higher rate of re-interventions.
原发性冠状动脉旁路移植术（CABG）后冠状动脉疾病（CAD）的进展较为常见，可能导致复发症状。各种数据表明，细胞凋亡是动脉粥样硬化斑块发展和进展过程中的主要事件。斑块血管平滑肌细胞（VSMC）比普通 VSMC 更容易受到 TP53 介导的凋亡。
我们研究了 192 名（18%为女性，年龄 60.9±7.4 岁）在 5 年前接受过原发性 CABG 的患者的 EDTA 血液。CAD 进展定义为临床终点：再手术（n=88；46%）、导管再介入（n=58；30%）或随访时心绞痛（n=89；46%）。通过 PCR-RFLP 研究了凋亡基因多态性（Toll 样受体 2 A753G、FAS 配体 C-844T、FAS 启动子 G-670A、TP53 Arg72Pro 和 CD14 C-260T），并与健康对照组（n=200，24%为女性，年龄 63.4±5.4）进行了比较。进行了性别特异性分析。
在 CAD 患者和健康对照组中，所有五种遗传多态性的杂合、纯合和野生型表达几乎完全相同。观察临床终点，Toll 样受体 2 多态性 GG 表达和 FAS 启动子多态性 GG 表达，结果显示复发性症状和再介入的相对风险增加（p=0.09）。FAS 启动子多态性 AA 表达的患者发生复发性症状的风险增加（n=28，p=0.04）。我们发现，TP53 多态性纯合表达的患者（n=3，均为男性）在先前 CABG 后需要再次介入的风险增加（p=0.03），但不需要再次手术。在长达 15 年的时间里，FAS LG、FAS 启动子和 TP53 纯合基因型的再介入率差异显著。
携带 FAS LG、FAS 启动子和 TP53 多态性的患者发生 CAD 进展的风险增加，因为他们的再介入率更高。
