MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification.
MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification.
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MicroRNA-32 促进血管平滑肌细胞钙化：作为冠状动脉钙化新标志物的意义
DOI：
10.1371/journal.pone.0174138
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zu X
中科院分区：
文献类型：
--
作者：
Liu J;Xiao X;Shen Y;Chen L;Xu C;Zhao H;Wu Y;Zhang Q;Zhong J;Tang Z;Liu C;Zhao Q;Zheng Y;Cao R;Zu X
心血管钙化是与心血管疾病相关的最严重的结果之一，通常导致显著的发病率和死亡率。先前的报道表明，表观基因组调控microRNAs （miRNAs）可能在血管平滑肌细胞（VSMC）钙化中起重要作用。在这里，我们确定了体内参与血管钙化的潜在关键mirna，并研究了miR-32-5p （miR-32）的作用。通过芯片分析，我们观察到在血管钙化的进展过程中miR-125b、miR-30a和miR-32的表达增加，miR-29a、miR-210和miR-320的表达减少。此外，miR-32的功能增益和功能丧失研究证实，miR-32通过增强体外骨形态发生蛋白-2、矮子相关转录因子-2（RUNX2）、骨桥蛋白和骨特异性磷酸化蛋白基质GLA蛋白的表达，促进小鼠VSMC钙化。此外，miR-32通过激活磷酸肌肽3-激酶（PI3K）信号，并通过靶向小鼠VSMCs中磷酸酶和紧张素同源Mrna （PTEN）的3 ' -未翻译区增加RUNX2的表达和磷酸化，从而调节血管钙化进程。此外，我们检测到冠心病合并冠状动脉钙化（CAC）患者血浆中miR-32水平高于非CAC患者（P = 0.016），进一步证实了miR-32是CAC的关键调节剂和潜在诊断标志物。
Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3′-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.