Costantino Sarah, Mohammed Shafeeq A, Ambrosini Samuele, Paneni Francesco
Center for Molecular Cardiology, University of Zürich, Zürich, Switzerland.
University Heart Center, Cardiology, University Hospital Zurich, Zürich, Switzerland.
Vasc Biol. 2020 May 15;2(1):H19-H28. doi: 10.1530/VB-20-0001. eCollection 2020.
Our genetic background provides limited information on individual risk of developing vascular complications overtime. New biological layers, namely epigenetic modifications, are now emerging as potent regulators of gene expression thus leading to altered transcriptional programs and vascular disease phenotypes. Such epigenetic modifications, defined as changes to the genome that do not involve changes in DNA sequence, are generally induced by environmental factors and poor lifestyle habits. Of note, adverse epigenetic signals acquired during life can be transmitted to the offspring thus leading to premature alterations of the epigenetic and transcriptional landscape eventually leading to early endothelial dysfunction and vascular senescence. Modifications of the epigenome play a pivotal role in the pathophysiology of cardiometabolic disturbances such as obesity and type 2 diabetes. In these patients, changes of DNA methylation and chromatin structure contribute to alter pathways regulating insulin sensitivity, glucose homeostasis, adipogenesis and vascular function. In this perspective, unveiling the 'epigenetic landscape' in cardiometabolic patients may help to identify new players implicated in obesity and diabetes-related vascular dysfunction and may pave the way for personalized therapies in this setting. In the present review, we discuss current knowledge of the epigenetic routes implicated in vascular damage and cardiovascular disease in patients with metabolic alterations.
我们的遗传背景提供的关于个体随时间推移发生血管并发症风险的信息有限。新的生物学层面，即表观遗传修饰，正作为基因表达的有力调节因子出现，从而导致转录程序和血管疾病表型的改变。这种表观遗传修饰被定义为基因组的变化，不涉及DNA序列的改变，通常由环境因素和不良生活习惯诱导。值得注意的是，生命过程中获得的不良表观遗传信号可传递给后代，从而导致表观遗传和转录格局的过早改变，最终导致早期内皮功能障碍和血管衰老。表观基因组的修饰在肥胖和2型糖尿病等心脏代谢紊乱的病理生理学中起关键作用。在这些患者中，DNA甲基化和染色质结构的变化有助于改变调节胰岛素敏感性、葡萄糖稳态、脂肪生成和血管功能的途径。从这个角度来看，揭示心脏代谢患者的“表观遗传格局”可能有助于识别与肥胖和糖尿病相关血管功能障碍有关的新因素，并可能为这种情况下的个性化治疗铺平道路。在本综述中，我们讨论了代谢改变患者中与血管损伤和心血管疾病相关的表观遗传途径的现有知识。
