College of Medicine, University of Sharjah, Sharjah, UAE.
Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE.
PLoS One. 2023 Mar 23;18(3):e0283608. doi: 10.1371/journal.pone.0283608. eCollection 2023.
Vitamin D3 deficiency, obesity, and diabetes mellitus (DM) have been shown to increase the risk of cardiovascular diseases (CVDs). However, the early detection of vascular damage in those patients is still difficult to ascertain. MicroRNAs (miRNAs) are recognized to play a critical role in initiation and pathogenesis of vascular dysfunction. Herein, we aimed to identify circulating miRNA biomarkers of vascular dysfunction as early predictors of CVDs. We have recruited 23 middle-aged Emiratis patients with the following criteria: A healthy control group with vitamin D ≥ 20ng, and BMI < 30 (C1 group = 11 individuals); A vitamin D deficiency (Vit D level ≤ 20 ng) and obese (BMI ≥ 30) group (A1 group = 9 patients); A vitamin D deficiency, obese, plus DM (A2 group = 3 patients). Arterial stiffness via pulse wave velocity (PWV) was measured and the whole transcriptome analysis with qPCR validation for miRNA in plasma samples were tested. PWV relative to age was significantly higher in A1 group 19.4 ± 4.7 m/s and A2 group 18.3 ± 1.3 m/s compared to controls 14.7 ± 2.1 m/s (p < 0.05). Similar patterns were also observed in the Augmentation pressure (AP) and Alx%. Whole RNA-Sequencing revealed miR-182-5p; miR-199a-5p; miR-193a-5p; and miR-155-5p were differentially over-expressed (logFC > 1.5) in high-risk patients for CVDs vs healthy controls. Collectively, our result indicates that four specific circulating miRNA signature, may be utilized as non-invasive, diagnostic and prognostic biomarkers for early vascular damage in patients suffering from vitamin D deficiency, obesity and DM.
维生素 D3 缺乏、肥胖和糖尿病 (DM) 已被证明会增加心血管疾病 (CVD) 的风险。然而，早期发现这些患者的血管损伤仍然难以确定。microRNAs (miRNAs) 被认为在血管功能障碍的起始和发病机制中发挥关键作用。在此，我们旨在确定血管功能障碍的循环 miRNA 生物标志物，作为 CVD 的早期预测指标。我们招募了 23 名中年阿联酋患者，入选标准如下：维生素 D≥20ng，BMI<30 的健康对照组 (C1 组=11 人)；维生素 D 缺乏 (Vit D 水平≤20ng) 和肥胖 (BMI≥30) 组 (A1 组=9 例)；维生素 D 缺乏、肥胖、加上 DM (A2 组=3 例)。通过脉搏波速度 (PWV) 测量动脉僵硬，并用 qPCR 验证血浆样本中的 miRNA 进行全转录组分析。A1 组的 PWV 相对年龄为 19.4±4.7m/s，A2 组为 18.3±1.3m/s，明显高于对照组的 14.7±2.1m/s(p<0.05)。在增宽压 (AP) 和 Alx% 中也观察到类似的模式。全 RNA 测序显示 miR-182-5p；miR-199a-5p；miR-193a-5p；和 miR-155-5p 在 CVD 高危患者中表达过度 (logFC>1.5)，与健康对照组相比。总之，我们的结果表明，四种特定的循环 miRNA 特征，可作为维生素 D 缺乏、肥胖和 DM 患者早期血管损伤的非侵入性、诊断和预后生物标志物。
