The complex pathobiology underlying cardiovascular diseases (CVDs) has yet to be explained. Aberrant epigenetic changes may result from alterations in enzymatic activities, which are responsible for putting in and/or out the covalent groups, altering the epigenome and then modulating gene expression. The identification of novel individual epigenetic-sensitive trajectories at single cell level might provide additional opportunities to establish predictive, diagnostic and prognostic biomarkers as well as drug targets in CVDs. To date, most of studies investigated DNA methylation mechanism and miRNA regulation as epigenetics marks. During atherogenesis, big epigenetic changes in DNA methylation and different ncRNAs, such as miR-93, miR-340, miR-433, miR-765, CHROME, were identified into endothelial cells, smooth muscle cells, and macrophages. During man development, lipid metabolism, inflammation and homocysteine homeostasis, alter vascular transcriptional mechanism of fundamental genes such as ABCA1, SREBP2, NOS, HIF1. At histone level, increased HDAC9 was associated with matrix metalloproteinase 1 (MMP1) and MMP2 expression in pro-inflammatory macrophages of human carotid plaque other than to have a positive effect on toll like receptor signaling and innate immunity. HDAC9 deficiency promoted inflammation resolution and reverse cholesterol transport, which might block atherosclerosis progression and promote lesion regression. Here, we describe main human epigenetic mechanisms involved in atherosclerosis, coronary heart disease, ischemic stroke, peripheral artery disease; cardiomyopathy and heart failure. Different epigenetics mechanisms are activated, such as regulation by circular RNAs, as MICRA, and epitranscriptomics at RNA level. Moreover, in order to open new frontiers for precision medicine and personalized therapy, we offer a panoramic view on the most innovative bioinformatic tools designed to identify putative genes and molecular networks underlying CVDs in man.

中文翻译：

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主要心血管疾病的个性化治疗中的表观遗传敏感途径。

心血管疾病（CVD）的复杂病理生物学尚未得到解释。异常的表观遗传变化可能是由酶活性的变化引起的，这些酶活性负责引入和/或释放共价基团，改变表观基因组，然后调节基因表达。在单细胞水平上鉴定新的个体表观遗传敏感性轨迹可能为建立预测性，诊断性和预后性生物标志物以及CVD中的药物靶标提供额外的机会。迄今为止，大多数研究都将DNA甲基化机制和miRNA调控作为表观遗传学标记。在动脉粥样硬化发生过程中，DNA甲基化和不同的ncRNA（例如miR-93，miR-340，miR-433，miR-765，CHROME）的表观遗传学变化被确认为内皮细胞，平滑肌细胞和巨噬细胞。在人类发育过程中，脂质代谢，炎症和高半胱氨酸稳态改变了基本基因如ABCA1，SREBP2，NOS，HIF1的血管转录机制。在组蛋白水平上，HDAC9的增加与人颈动脉斑块促炎性巨噬细胞中基质金属蛋白酶1（MMP1）和MMP2的表达有关，而不是对诸如受体信号转导和先天免疫的收费产生积极影响。HDAC9缺乏促进炎症消退并逆转胆固醇转运，这可能会阻止动脉粥样硬化的进展并促进病变消退。在这里，我们描述了涉及动脉粥样硬化，冠心病，缺血性中风，外周动脉疾病的主要人类表观遗传机制；心肌病和心力衰竭。激活了不同的表观遗传学机制，例如通过环状RNA（如MICRA）进行调控，以及在RNA水平上的转录组学。此外，为了开创精密医学和个性化治疗的新领域，我们提供了最新颖的生物信息学工具的全景图，这些工具旨在识别人类CVD的推定基因和分子网络。