A Chymase Inhibitory RNA Aptamer Improves Cardiac Function and Survival after Myocardial Infarction
A Chymase Inhibitory RNA Aptamer Improves Cardiac Function and Survival after Myocardial Infarction
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DOI：
10.1016/j.omtn.2018.11.001
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发表时间：
2019-03-01
影响因子：
8.8
通讯作者：
Nakamura, Yoshikazu
中科院分区：
文献类型：
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作者：
Jin, Denan;Takai, Shinji;Nakamura, Yoshikazu
我们已经报道，肥大细胞糜酶，血管紧张素II生成酶，是重要的心血管组织。最近，我们开发了一种新的凝乳酶特异性抑制RNA适体，HA28，我们评估了HA28对心功能和心肌梗死后死亡率的影响。心肌梗死后HA28治疗可显著改善超声心动图参数，如左心室射血分数、短轴缩短率和早期与晚期心室充盈速度的比值。在HA28治疗组中死亡率显著降低。心脏糜酶活性和糜酶基因表达在媒介物处理的心肌梗死组中显著更高，并且这些在HA 28处理的心肌梗死组中被显著抑制。本研究提供了第一个证据表明，一个单链RNA适体，是一个凝乳酶特异性抑制剂是非常有效的治疗心肌梗死引起的急性心力衰竭。糜酶可能成为心肌梗死后病理生理学研究的新靶点。
We have reported that mast cell chymase, an angiotensin II-generating enzyme, is important in cardiovascular tissues. Recently, we developed a new chymase-specific inhibitory RNA aptamer, HA28, and we evaluated the effects of HA28 on cardiac function and the mortality rate after myocardial infarction. Echocardiographic parameters, such as the left ventricular ejection fraction, fractional shortening, and the ratio of early to late ventricular filling velocities, were significantly improved by treatment with HA28 after myocardial infarction. The mortality rate was significantly reduced in the HA28-treated group. Cardiac chymase activity and chymase gene expression were significantly higher in the vehicle-treated myocardial infarction group, and these were markedly suppressed in the HA28-treated myocardial infarction group. The present study provides the first evidence that a single-stranded RNA aptamer that is a chymase-specific inhibitor is very effective in the treatment of acute heart failure caused by myocardial infarction. Chymase may be a new therapeutic target in post-myocardial infarction pathophysiology.