Abstract：
Coronary artery disease (CAD) and its main complication, myocardial infarction (MI), is a complex disease caused by environmental and genetic factors and their interaction. Family-based linkage analysis and genome-wide association studies have indicated many of genetic variations related to CAD and MI in recent years. Some are in the coding sequence, which mediates the coding protein, while others are in the non-coding region, which affects the expression of adjacent genes and forms differential gene expression. These variants and differential expressions will have varying degrees of impact on the development of the cardiovascular system and normal heart electrical activity function, subsequently leading to CAD and MI. Among these affected genes, some Transcription Factors (TFs), as important means of transcriptional regulation, have a key role in the pathogenesis of coronary artery disease and myocardial infarction. The GATAs binding protein 2 (GATA2) enhances monocyte adhesion and promoted vessel wall permeabilization through vascular EC adhesion molecule 1 (VCAM-1) upregulation, further revealing its atherosclerosis-promoting role. Myocyte enhancer factor 2 (MEF2) has a role in fostering many functions of the atherosclerotic endothelium and is a potential therapeutic target for atherosclerosis, thrombosis, and inflammation. Nuclear factor-kappa B (NF-κB) is an important promoter of vascular endothelial growth factor (VEGF)-driven angiogenesis, and its pathway has a key role in atherosclerosis-related complications such as angiogenesis, inflammation, apoptosis, and immune effects. Activating transcription factor 3 (ATF3) may be a novel prognostic biomarker and therapeutic target for atherosclerosis. The important role of signal transducer and activator of transcription 3 (STAT3) (especially in mitochondria) in endothelial cells (EC) dysfunction, inflammation, macrophage polarization and immunity in atherosclerosis.
摘要：
冠状动脉疾病（CAD）及其主要并发症，心肌梗死（MI），是一种由环境和遗传因素及其相互作用引起的复杂疾病。近年来，基于家庭的连锁分析和全基因组关联研究表明许多与CAD和MI相关的遗传变异。有些在编码序列中，介导编码蛋白，而其他人在非编码区，影响相邻基因的表达并形成差异基因表达。这些变异和差异表达会对心血管系统的发育和正常心脏电活动功能产生不同程度的影响,随后导致CAD和MI。在这些受影响的基因中，一些转录因子（TFs），作为转录调控的重要手段，在冠心病和心肌梗死的发病机制中起着关键作用。GATAs结合蛋白2（GATA2）通过血管EC粘附分子1（VCAM-1）上调增强单核细胞粘附并促进血管壁透化，进一步揭示其对动脉粥样硬化的促进作用。肌细胞增强因子2（MEF2）在促进动脉粥样硬化内皮的许多功能中起作用，是动脉粥样硬化的潜在治疗靶标，血栓形成,和炎症。核因子-κB（NF-κB）是血管内皮生长因子（VEGF）驱动的血管生成的重要启动子，其途径在动脉粥样硬化相关并发症如血管生成中起关键作用，炎症,凋亡，和免疫效果。激活转录因子3（ATF3）可能是动脉粥样硬化的新型预后生物标志物和治疗靶标。信号转导和转录激活因子3(STAT3)(尤其是线粒体)在内皮细胞(EC)功能障碍中的重要作用,炎症,动脉粥样硬化中的巨噬细胞极化和免疫。
