Molecular markers of cardiac fibrosis after myocardial infarction

O. Barbarash, A. Kutikhin, T. Pecherina, R. Tarasov, V. Kashtalap, N. Fedorova, L. Bogdanov, O. Hryachkova, D. Sedykh
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Abstract

Aim. To perform a screening for molecular markers of cardiac fibrosis upon myocardial infarction.Materials and Methods. We carried out echocardiography-guided endomyocardial biopsy of affected and intact interventricular septum segments of 7 patients with anterior myocardial infarction. Fibrotic and adjacent intact cardiac tissue was dissected into 2 equal segments and: 1) homogenized with the further RNA extraction, reverse transcription, and quantitative polymerase chain reaction; 2) fixed in formalin and embedded into paraffin with the further van Gieson staining for the histological verification of cardiac fibrosis.Results. We found that the expression of ACTA2, VIM, CTGF, COL1A1, TGFB1, TGFBR1, AGTR1, CCL2 and TNF genes in fibrotic cardiac tissue was ≥ 3-fold higher as compared with the adjacent intact myocardium reflective of active extracellular matrix production by fibroblast-derived myofibroblasts.Conclusion. We have for the first time shown AGTR1, CCL2, and TNF genes as candidates for post-infarction cardiac fibrosis in addition to ACTA2, VIM, CTGF, COL1A1, TGFB1, and TGFBR1 genes.
心肌梗死后心肌纤维化的分子标记
的目标。筛选心肌梗死后心肌纤维化的分子标志物。材料与方法。我们对7例前路心肌梗死患者行超声心动图引导下的室间隔病变及完整段心内膜活检。将纤维化和邻近的完整心脏组织切成2个相等的片段,1)进一步提取RNA,进行反转录和定量聚合酶链反应,使其均质;2)用福尔马林固定,石蜡包埋,进一步进行van Gieson染色,进行心肌纤维化组织学验证。我们发现,心肌纤维化组织中ACTA2、VIM、CTGF、COL1A1、TGFB1、TGFBR1、AGTR1、CCL2和TNF基因的表达比邻近完整心肌高3倍以上,反映成纤维细胞来源的肌成纤维细胞产生活跃的细胞外基质。我们首次发现除了ACTA2、VIM、CTGF、COL1A1、TGFB1和TGFBR1基因外,AGTR1、CCL2和TNF基因也是梗死后心脏纤维化的候选基因。
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