First Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
PLoS One. 2012;7(11):e50054. doi: 10.1371/journal.pone.0050054. Epub 2012 Nov 21.
Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.
Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1(st) day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6).
In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.
尽管在诊断和治疗方面取得了重大进展,但急性心肌梗死(MI)仍是普通人群死亡的主要原因。通过研究基因表达获得的对心肌梗死病理生理学的新认识,应该有助于发现 MI 的新型生物标志物,并提出新的治疗策略。我们的研究目的是确定急性心肌梗死患者白细胞中的基因表达模式。
纳入 28 例 ST 段抬高型心肌梗死(STEMI)患者。在心肌梗死的第 1 天、第 4-6 天和第 6 个月采集血液。对照组包括 14 例稳定型冠心病患者,无心肌梗死病史。使用 Affymetrix Human Gene 1.0 ST 微阵列和 GCS3000 TG 系统进行基因表达分析。将表达水平改变(倍数变化>1.5,p<0.05)的基因列表提交给 Ingenuity Pathway Analysis。检查每组的基因列表,以确定经典途径和分子及细胞功能。将急性心肌梗死的急性期与同一患者的 6 个月后的稳定期(稳定期)和对照组进行比较,发现 24 个基因表达发生变化。在经典分析中,有 3 条途径被突出显示:PPAR(过氧化物酶体增殖物激活受体)、IL-10 和 IL-6(白细胞介素 10 和 6)的信号传导。
在 STEMI 的急性期,与脂质/葡萄糖代谢、血小板功能和动脉粥样硬化斑块稳定性相关的多个途径的数十个基因表现出改变的表达。在心肌梗死后的最初几天,绝大多数患者观察到 SOCS3 和 FAM20 基因的上调。