Discipline of Laboratory Medicine, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
Discipline of Laboratory Medicine, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
Drug Discov Today. 2018 Mar;23(3):719-726. doi: 10.1016/j.drudis.2018.01.004. Epub 2018 Jan 9.
The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications. Targeting these epigenetic changes could provide a new avenue for the treatment of pathological blood clots. However, the lack of tissue specificity warrants high-resolution genomic studies of the transcriptome and methylome that will reveal explicit epigenetic targets for the design of superior drugs with minimum off-target effects.
止血系统受到严密的调控以维持体内平衡，避免出现不必要的出血或血栓并发症。最近的研究强调了表观遗传变化（如 DNA 甲基化、组蛋白修饰和 miRNA 机制）的重要性，这些变化会改变基因表达。这可能导致止血或血管表达分子失调，从而导致血栓并发症的发展。针对这些表观遗传变化可能为病理性血栓的治疗提供新途径。然而，由于缺乏组织特异性，需要对转录组和甲基组进行高分辨率基因组研究，这将揭示明确的表观遗传靶标，以设计具有最小脱靶效应的优越药物。
