BACKGROUND Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. Vascular epithelial growth factor receptor-1 (VEGFR-1) stimulates angiogenesis and vascular permeability, and functions as a decoy to sequester VEGF and prevent initiation of intracellular signaling. VEGFR-1 knockout mice exhibit significantly higher mortality due to heart failure, cardiac hypertrophy, and cardiac dysfunction. An evident increase in macrophage infiltration and cardiac fibrosis are also observed after transverse aortic constriction. Therefore, VEGFR-1 gene variants may be involved in CAD. In this study, VEGFR-1 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients and ethnic-matched controls. RESULTS A total of 16 DNA sequence variants (DSVs) including six single-nucleotide polymorphisms (SNPs) were found in the VEGFR-1 gene promoter and 5'-untranslated region. Five novel DSVs and one SNP were only identified in AMI patients group. These DSVs and SNP significantly altered the transcriptional activity of the VEGFR-1 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the DSVs and SNPs evidently affected the binding of transcription factors. CONCLUSIONS The genetic variants in VEGFR-1 gene identified in AMI patients may alter the transcriptional activity of the VEGFR-1 gene promoter and change VEGFR-1 level, contributing to AMI development.

中文翻译：

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急性心肌梗死中VEGFR-1基因启动子的遗传变异。

背景技术包括急性心肌梗塞（AMI）的冠状动脉疾病（CAD）是由动脉粥样硬化引起的常见的复杂疾病。血管上皮生长因子受体1（VEGFR-1）刺激血管生成和血管通透性，并起诱捕作用，隔离VEGF并阻止细胞内信号传导的启动。由于心力衰竭，心脏肥大和心脏功能障碍，VEGFR-1基因敲除小鼠表现出明显更高的死亡率。横断主动脉缩窄后也观察到巨噬细胞浸润和心脏纤维化明显增加。因此，VEGFR-1基因变异可能与CAD有关。在这项研究中，在大型AMI患者和种族匹配的对照人群中对VEGFR-1基因启动子进行了基因和功能分析。结果在VEGFR-1基因启动子和5'-非翻译区共发现16个DNA序列变异体（DSV），包括6个单核苷酸多态性（SNP）。仅在AMI患者组中鉴定出5种新颖的DSV和1种SNP。这些DSV和SNP显着改变了HEK-293和H9c2细胞中VEGFR-1基因启动子的转录活性（P <0.05）。进一步的电泳迁移率迁移分析表明，DSV和SNP明显影响转录因子的结合。结论在AMI患者中鉴定出的VEGFR-1基因的遗传变异可能会改变VEGFR-1基因启动子的转录活性并改变VEGFR-1水平，从而促进AMI的发展。仅在AMI患者组中鉴定出5种新颖的DSV和1种SNP。这些DSV和SNP显着改变了HEK-293和H9c2细胞中VEGFR-1基因启动子的转录活性（P <0.05）。进一步的电泳迁移率迁移分析表明，DSV和SNP明显影响转录因子的结合。结论在AMI患者中鉴定出的VEGFR-1基因的遗传变异可能会改变VEGFR-1基因启动子的转录活性并改变VEGFR-1水平，从而促进AMI的发展。仅在AMI患者组中鉴定出5种新颖的DSV和1种SNP。这些DSV和SNP显着改变了HEK-293和H9c2细胞中VEGFR-1基因启动子的转录活性（P <0.05）。进一步的电泳迁移率迁移分析表明，DSV和SNP明显影响转录因子的结合。结论在AMI患者中鉴定出的VEGFR-1基因的遗传变异可能会改变VEGFR-1基因启动子的转录活性并改变VEGFR-1水平，从而促进AMI的发展。进一步的电泳迁移率迁移分析表明，DSV和SNP明显影响转录因子的结合。结论在AMI患者中鉴定出的VEGFR-1基因的遗传变异可能会改变VEGFR-1基因启动子的转录活性并改变VEGFR-1水平，从而促进AMI的发展。进一步的电泳迁移率迁移分析表明，DSV和SNP明显影响转录因子的结合。结论在AMI患者中鉴定出的VEGFR-1基因的遗传变异可能会改变VEGFR-1基因启动子的转录活性并改变VEGFR-1水平，从而促进AMI的发展。