Fontanella Rosaria Anna, Scisciola Lucia, Rizzo Maria Rosaria, Surina Surina, Sardu Celestino, Marfella Raffaele, Paolisso Giuseppe, Barbieri Michelangela
Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Mediterrannea Cardiocentro, Naples, Italy.
Front Cardiovasc Med. 2021 Nov 19;8:768026. doi: 10.3389/fcvm.2021.768026. eCollection 2021.
In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.
在肥胖症中，包括组蛋白重塑、DNA甲基化和微小RNA在内的多种表观遗传修饰可能会累积，并导致炎症分子（即脂肪因子）的表达增加，而这些脂肪因子反过来可能会诱导或加速心血管和代谢紊乱的发生与发展。为了更好地阐明脂肪因子调节炎症反应的潜在表观遗传机制，我们使用基于焦磷酸测序的定量分析方法，对356名健康受试者外周血白细胞中白细胞介素-6（IL-6）和核因子-κB（NF-κB）基因启动子区域的DNA甲基化谱以及血浆微小RNA-21水平进行了评估，并将其与血浆脂联素水平、体脂含量和主要促炎标志物进行关联分析。此外，还对DNA甲基化谱和血浆微小RNA-21水平与内膜中层厚度（IMT，早期动脉粥样硬化替代标志物）、左心室质量（LVM）、左心室射血分数（LVEF）和心脏功能指数（MPI）进行了相关性分析，以评估其在心血管结局方面的任何潜在临床意义。研究结果证实了表观遗传学在肥胖相关心血管并发症中的作用，并首次支持血浆微小RNA-21以及有核血细胞中IL-6和NF-κB DNA甲基化变化作为预测肥胖症心血管风险潜在生物标志物的潜在作用。此外，我们的研究结果表明脂联素在预防肥胖受试者脂肪组织含量增加所诱导的表观遗传修饰中发挥作用，为脂联素的抗炎特性和心血管益处的潜在机制提供了新证据。血细胞中发现的肥胖相关表观遗传修饰的确切机制，以及类似的表观遗传变化是否反映脂肪和心肌组织修饰，需要在未来的实验中进一步研究。
