Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Epigenetics. 2022 Jan;17(1):93-109. doi: 10.1080/15592294.2021.1876285. Epub 2021 Jan 25.
Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are , and . Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are , and . Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.
肥胖是心血管疾病的一个主要危险因素。血液检测到的表观遗传谱可以作为非侵入性的临床相关生物标志物。因此，我们研究了肥胖受试者和瘦对照者外周血中参与炎症的基因的 DNA 甲基化及其与心血管代谢测量的相关性。我们从肥胖症患者（n=24）和对照成年人（n=24）中获得了血液和脂肪组织（AT）样本。分离的 AT 小动脉用于检测血流诱导的扩张（FID）和一氧化氮（NO）和活性氧（ROS）的产生。通过多普勒超声测量肱动脉血流介导的扩张（FMD）。分析了全血 DNA 中 94 个与血管功能和心血管代谢危险因素相关的炎症和自身免疫基因的启动子甲基化。与肥胖受试者相比，77 个基因在对照中具有更高的甲基化分数，而 28 个促炎基因在肥胖个体中明显低甲基化；其中包括基因和。这些基因中有 15 个在肥胖受试者中的 mRNA 明显高于对照；其中包括基因和。与 BMI、总脂肪%、内脏脂肪%、血压、空腹血浆胰岛素、血清 IL6 和 C 反应蛋白、小动脉 ROS 和酒精消耗呈负相关，与 lean%、HDL、血浆叶酸和维生素 B12、小动脉 FID 和 NO 产生以及肱动脉 FMD 呈正相关。我们的结果表明，肥胖成年人的血管功能障碍可能归因于全身性低甲基化和免疫相关基因的过度表达。
