Department of Cardiology, Xi'an No.1 hospital, Xi'an, China.
Department of Cardiology, Xi'an No.4 hospital, Xi'an, China.
J Clin Lab Anal. 2020 Jun;34(6):e23246. doi: 10.1002/jcla.23246. Epub 2020 Feb 28.
Metabolically healthy obese patients accounts for a large part of obese population, but its clinical significance and cardiac dysfunction are often underestimated. The microRNA profiles of metabolically healthy obese patients were investigated in the study, and the selected microRNA (miRNA) based on our microarray assay will be further verified in a relatively large metabolically healthy obese population.
microRNA microarray was performed from six metabolically healthy obese and 6 health control blood samples. Based on the bioinformatics analysis, we further measured RT-PCR, fibrosis markers, echocardiograms, and TGF-β1/Smad signaling pathway in 600 metabolically healthy obese population.
We found that miRNAs expression characteristics in metabolically healthy obese groups were markedly different from healthy control group. MiRNA-21 was significantly increased in the samples of metabolically healthy obese patients. Besides, miRNA-21 levels were associated with cardiac fibrosis marker. Meanwhile, higher miRNA-21 levels were related to elevated E/E'. Besides, patients with the highest miRNA-21 quartile showed the lowest ratio of E/A. These associations between miRNA-21 and diastolic function parameters were independent of obesity and other confounding variables. Of note, TGF-β1and Smad 3 were significantly upregulated while Smad 7 was downregulated according to the miRNA-21 quartiles in metabolically healthy obese group.
We demonstrated the profiles of circulating microRNAs in metabolically healthy obese patients. Increased plasma miRNA-21 levels were related to impaired diastolic function independent of other relevant confounding variables. MiRNA-21 could be one of the mechanistic links between obesity and diastolic dysfunction through regulating cardiac fibrosis via TGF-β1/Smad signaling pathway in obese hearts, which may serve as a novel target of disease intervention.
代谢健康型肥胖患者在肥胖人群中占很大比例，但常被低估其临床意义和心功能障碍。本研究旨在研究代谢健康型肥胖患者的 microRNA 谱，并进一步在相对较大的代谢健康型肥胖人群中验证基于我们的微阵列分析选择的 microRNA（miRNA）。
对 6 例代谢健康型肥胖者和 6 例健康对照者的血液样本进行 microRNA 微阵列分析。基于生物信息学分析，我们进一步在 600 例代谢健康型肥胖人群中测量 RT-PCR、纤维化标志物、超声心动图和 TGF-β1/Smad 信号通路。
我们发现代谢健康型肥胖组的 miRNAs 表达特征与健康对照组明显不同。miRNA-21 在代谢健康型肥胖患者的样本中显著增加。此外，miRNA-21 水平与心脏纤维化标志物相关。同时，miRNA-21 水平较高者的 E/E'也较高。此外，miRNA-21 四分位间距最高的患者的 E/A 比值最低。这些 miRNA-21 与舒张功能参数之间的关联独立于肥胖和其他混杂变量。值得注意的是，根据代谢健康型肥胖组的 miRNA-21 四分位间距，TGF-β1 和 Smad 3 显著上调，而 Smad 7 下调。
我们证明了代谢健康型肥胖患者循环 microRNAs 的特征。血浆中 miRNA-21 水平升高与其他相关混杂因素无关，与舒张功能障碍有关。miRNA-21 可能通过调节肥胖心脏中的 TGF-β1/Smad 信号通路引起的心脏纤维化，成为肥胖与舒张功能障碍之间的机制联系之一，可作为疾病干预的新靶点。
