Ranasinghe A Dushani C U, Schwarz Margaret A
Harper Cancer Research Institute, United States; Departments of Pediatrics and Anatomy, Indiana University School of Medicine, South Bend, IN, United States.
Harper Cancer Research Institute, United States; Department of Chemistry and Biochemistry, University of Notre Dame, United States; Departments of Pediatrics and Anatomy, Indiana University School of Medicine, South Bend, IN, United States; Cell Biology & Physiology, Indiana University School of Medicine, South Bend, IN, United States.
Biochem Pharmacol. 2022 Oct;204:115245. doi: 10.1016/j.bcp.2022.115245. Epub 2022 Sep 10.
Pulmonary arterial hypertension (PAH) is a devastating vascular disease with multiple etiologies. Emerging evidence supports a fundamental role for epigenetic machinery and metabolism in the initiation and progression of PAH. Here, we summarize emerging epigenetic mechanisms that have been identified as contributors to PAH evolution, specifically, DNA methylation, histone modifications, and microRNAs. Furthermore, the interplay between epigenetics with metabolism is explored while new crosstalk targets to be investigated in PAH are proposed that highlight multi-omics strategies including integrated epigenomics and metabolomics. Therapeutic opportunities and challenges associated with epigenetics and metabolomics in PAH are examined, highlighting the role that epigenetics and metabolomics have in facilitating early detection, personalized dietary plans, and advanced drug therapy for PAH.
肺动脉高压(PAH)是一种具有多种病因的毁灭性血管疾病。新出现的证据支持表观遗传机制和代谢在PAH的发生和发展中起重要作用。在此,我们总结了已被确定为PAH演变促成因素的新表观遗传机制,具体包括DNA甲基化、组蛋白修饰和微小RNA。此外,还探讨了表观遗传学与代谢之间的相互作用,同时提出了PAH中有待研究的新的相互作用靶点,这些靶点突出了包括综合表观基因组学和代谢组学在内的多组学策略。研究了PAH中与表观遗传学和代谢组学相关的治疗机会和挑战,强调了表观遗传学和代谢组学在促进PAH的早期检测、个性化饮食计划和先进药物治疗方面的作用。