Biochemistry Department, King Abdulaziz University, P.O. Box 80218, Jeddah 21589, Saudi Arabia.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Int J Mol Sci. 2024 Jul 25;25(15):8087. doi: 10.3390/ijms25158087.
Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated following metformin therapy. Inflammatory and vascular markers were measured in 29 individuals with T1DM and 20 matched healthy controls (HCs). miR-199b-5p expression in CFU-Hill's colonies was analyzed from each study group, and correlations with inflammatory/vascular health indices were evaluated. Significant upregulation of miR-199b-5p was observed in T1DM, which was significantly downregulated by metformin. miR-199b-5p correlated positively with vascular endothelial growth factor-D and c-reactive protein (CRP: nonsignificant). ROC analysis determined miR-199b-5p to define subclinical CVD by discriminating between HCs and T1DM individuals. ROC analyses of HbA1c and CRP showed that the upregulation of miR-199b-5p in T1DM individuals defined subclinical CVD at HbA1c > 44.25 mmol and CRP > 4.35 × 10 pg/mL. Ingenuity pathway analysis predicted miR-199b-5p to inhibit the target genes , , and . Metformin was predicted to downregulate miR-199b-5p via NFATC2 and STAT3 and reverse its downstream effects. This study validated the antiangiogenic properties of miR-199b-5p and substantiated miR-199b-5p overexpression as a biomarker of subclinical CVD. The downregulation of miR-199b-5p by metformin confirmed its cardio-protective effect.
已控制的 1 型糖尿病（T1DM）的特征是炎症和内皮功能障碍，因此构成亚临床心血管疾病（CVD）的合适模型。在小鼠 CVD 中过表达 miR-199b-5p 显示出促动脉粥样硬化作用。我们假设 miR-199b-5p 在亚临床 CVD 中过度表达，但在用二甲双胍治疗后会下调。在 29 名 T1DM 患者和 20 名匹配的健康对照者（HCs）中测量了炎症和血管标志物。分析了每组研究中的 CFU-Hill 集落中的 miR-199b-5p 表达，并评估了其与炎症/血管健康指标的相关性。在 T1DM 中观察到 miR-199b-5p 的显著上调，而二甲双胍可显著下调其表达。miR-199b-5p 与血管内皮生长因子-D 和 C 反应蛋白（CRP：无显著性）呈正相关。ROC 分析确定 miR-199b-5p 通过区分 HCs 和 T1DM 个体来定义亚临床 CVD。miR-199b-5p 在 T1DM 个体中的上调，根据 HbA1c>44.25mmol 和 CRP>4.35×10pg/ml 定义亚临床 CVD 的 ROC 分析。IPA 分析预测 miR-199b-5p 抑制靶基因 、 、和 。二甲双胍通过 NFATC2 和 STAT3 预测下调 miR-199b-5p，并逆转其下游效应。本研究验证了 miR-199b-5p 的抗血管生成特性，并证实了 miR-199b-5p 的过度表达作为亚临床 CVD 的生物标志物。二甲双胍下调 miR-199b-5p 证实了其心脏保护作用。
