MicroRNAs Are Associated with Uremic Toxicity, Cardiovascular Calcification, and Disease
MicroRNAs Are Associated with Uremic Toxicity, Cardiovascular Calcification, and Disease
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DOI：
10.1159/000450774
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Metzinger, Laurent
中科院分区：
文献类型：
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作者：
Massy, Ziad A.;Metzinger-Le Meuth, Valerie;Metzinger, Laurent
背景资料：血管钙化已被认为是慢性肾脏病（CKD）和下游心血管并发症的主要风险因素。microRNAs（miRNAs）是一种由2025个核苷酸组成的小的非编码RNA，通过抑制或降解靶mRNA来调节基因表达，并构成潜在的新生物标志物和未来的治疗策略.总结：我们测试了几种cardiovascularspecific miRNAs作为CKD、心血管疾病和心血管并发症的新生物标志物的相关性.我们在小鼠模型中发现，在CKD和动脉粥样硬化的关键阶段，miR-126、miR-143、miR-145和miR-223水平及其特异性靶点的水平受到调节。此外，miRNA水平与CKD和动脉粥样硬化的经典生物标志物如胆固醇、尿素和钙水平相关。在CKD、血液透析和肾移植受者的血清中观察到这些相同miRNA的失调。我们还证明了血清miRNAs和尿毒症毒素之间的相关性。因此，我们认为miR-126，miR-143，miR-145和miR-223是血管钙化和与CKD.Key消息相关的心血管疾病的潜在生物标志物：识别新的生物标志物，可以改善CKD和心血管疾病患者的诊断和监测在现代医学中至关重要。我们的数据可能在与CKD相关的心血管疾病的管理中特别有用，为了解心血管疾病和心血管钙化的分子事件提供了新的思路，并可能用作预防这些疾病的治疗策略。(c)2017 S. Karger AG，巴塞尔
Background: Vascular calcification has been recognized to be a major risk factor in chronic kidney disease (CKD) and downstream cardiovascular complications. MicroRNAs (miRNAs) are small noncoding RNAs comprising 2025 nucleotides that regulate gene expression by inhibiting or degrading the target mRNA, and constitute potential new biomarkers and future therapeutic strategies.Summary: We tested the relevance of several cardiovascularspecific miRNAs as new biomarkers for CKD, cardiovascular disease, and cardiovascular complications. We have shown, in murine models, that miR-126, miR-143, miR-145, and miR-223 levels and the levels of their specific targets are modulated during the crucial stages of CKD and atherosclerosis. In addition, miRNA levels were correlated with classical biomarkers of CKD and atherosclerosis such as cholesterol, urea, and calcium levels. Dysregulation of these same miRNAs was observed in the serum of CKD, hemodialyzed, and kidney transplant recipients. We also demonstrated correlations between serum miRNAs and uremic toxins. We therefore suggest that miR-126, miR143, miR-145, and miR-223 are potential biomarkers of vascular calcification and cardiovascular disease associated with CKD.Key Messages: The identification of new biomarkers that can improve the diagnosis and monitoring of CKD and cardiovascular disease patients is crucial in modern medicine. Our data could be particularly useful in the management of cardiovascular disease associated with CKD, provide new light in the understanding of the molecular events underlying cardiovascular disease and cardiovascular calcification, and possibly be used as a treatment strategy to prevent these diseases. (c) 2017 S. Karger AG, Basel