Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes.
Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes.
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DOI：
10.1038/s41598-017-00070-6
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Llorente-Cortes V
中科院分区：
文献类型：
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作者：
de Gonzalo-Calvo D;van der Meer RW;Rijzewijk LJ;Smit JW;Revuelta-Lopez E;Nasarre L;Escola-Gil JC;Lamb HJ;Llorente-Cortes V
我们利用体外、体内和基于患者的方法，研究了循环 microRNA (miRNA) 作为心肌脂肪变性（糖尿病心肌病的一个标志）的替代生物标志物的潜力。我们分析了控制良好且已证实不存在结构性心脏病或诱导性缺血的 2 型糖尿病患者的血清中富含心肌细胞的 miRNA 特征，以及相同年龄范围和 BMI (N = 86) 的对照志愿者、高脂饮食喂养小鼠模型的血清以及脂质负载 HL-1 的外泌体中的心肌细胞富集 miRNA 特征。 心肌细胞。循环 miR-1 和 miR-133a 水平与 2 型糖尿病患者的心肌脂肪变性密切相关，独立于线性和逻辑回归分析中的混杂因素（所有模型的 P<0.050）。与心肌脂肪变性类似，2型糖尿病患者的miR-133a水平较健康受试者升高（P<0.050）。与对照动物相比，高脂饮食喂养的小鼠的循环 miR-1 和 miR-133a 水平显着升高（P<0.050），显示出更高的心肌脂肪变性。负载脂质的 HL-1 心肌细胞释放的外泌体中 miR-1 和 miR-133a 水平较高（P<0.050）。循环 miR-1 和 miR-133a 是心肌脂肪变性的独立预测因子。我们的结果强调了循环 miRNA 作为亚临床糖尿病心肌病诊断工具的价值。
Using in vitro, in vivo and patient-based approaches, we investigated the potential of circulating microRNAs (miRNAs) as surrogate biomarkers of myocardial steatosis, a hallmark of diabetic cardiomyopathy. We analysed the cardiomyocyte-enriched miRNA signature in serum from patients with well-controlled type 2 diabetes and with verified absence of structural heart disease or inducible ischemia, and control volunteers of the same age range and BMI (N = 86), in serum from a high-fat diet-fed murine model, and in exosomes from lipid-loaded HL-1 cardiomyocytes. Circulating miR-1 and miR-133a levels were robustly associated with myocardial steatosis in type 2 diabetes patients, independently of confounding factors in both linear and logistic regression analyses (P < 0.050 for all models). Similar to myocardial steatosis, miR-133a levels were increased in type 2 diabetes patients as compared with healthy subjects (P < 0.050). Circulating miR-1 and miR-133a levels were significantly elevated in high-fat diet-fed mice (P < 0.050), which showed higher myocardial steatosis, as compared with control animals. miR-1 and miR-133a levels were higher in exosomes released from lipid-loaded HL-1 cardiomyocytes (P < 0.050). Circulating miR-1 and miR-133a are independent predictors of myocardial steatosis. Our results highlight the value of circulating miRNAs as diagnostic tools for subclinical diabetic cardiomyopathy.