Serum microRNA-30d is a sensitive biomarker for angiotensin II-induced cardiovascular complications in rats
Serum microRNA-30d is a sensitive biomarker for angiotensin II-induced cardiovascular complications in rats
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DOI：
10.1007/s00380-021-01853-8
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发表时间：
2021-04-16
影响因子：
1.5
通讯作者：
Ono, Katsushige
中科院分区：
文献类型：
--
作者：
Morishima, Masaki;Ono, Katsushige
我们测试的假设，血管紧张素II（Ang II）诱导的心血管并发症是从什么样的儿茶酚胺诱导的血清循环生物标志物在大鼠中区分。输注Ang II（1.68 mg/kg/d）显著增加了第1周或之后评估的收缩压和舒张压，并伴有心脏/体重比的增加。去甲肾上腺素输注（5.40 mg/kg/天）产生了相似程度的高血压，但没有增加心脏重量。Ang II诱导的高血压与血清microRNA-30 d（miR-30 d）的急剧上调数百倍有关，伴随着心房中miR-30 d水平的增加，但心室中没有。Ang Ⅱ可显著增加心房组织中脑钠肽（BNP）的mRNA表达，而去甲肾上腺素则无此作用。使用大鼠新生心肌细胞的体外研究表明，BNP在培养基中应用6 h或更长时间时，会导致miR-30 d的增加。体外应用Ang II增加了细胞大小，尽管BNP和miR-30 d无法模拟Ang II的作用。我们的结论是，血清循环microRNA-30 d是一个敏感的生物标志物血管紧张素II诱导的心血管并发症。也有人推测，血管紧张素II诱导的心肌细胞肥大可能是独立的miR-30 d/BNP信号通路。
We tested the hypothesis that angiotensin II (Ang II)-induced cardiovascular complications are distinguished from what catecholamine-induced by their serum circulating biomarkers in rats. Infusion of Ang II (1.68 mg/kg/day) significantly increased systolic and diastolic blood pressure assessed at week one or later, accompanied by an increase of heart/body weight ratio. Noradrenaline infusion (5.40 mg/kg/day) produced a similar degree of hypertension, but did not increase heart weight. Ang II-, but not noradrenaline-induced hypertension was associated with a drastic upregulation of serum microRNA-30d (miR-30d) by hundreds of times, accompanied by an increase of miR-30d levels in the atrium but not in the ventricle. Ang II, but not noradrenaline, significantly increased mRNA of brain natriuretic peptide (BNP) in the atrium. Studies using rat neonatal cardiomyocytes in vitro demonstrated that BNP caused an increase of miR-30d when applied for 6 h or longer in the culture medium. In vitro application of Ang II increased the cell size, although BNP and miR-30d were unable to mimic the effect of Ang II. We conclude that serum circulating microRNA-30d is a sensitive biomarker for Ang II-induced cardiovascular complications. It is also postulated that Ang II-induced cardiomyocyte hypertrophy could be independent of miR-30d/BNP signaling pathways.