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.

我们已经报道了肥大细胞糜酶，一种血管紧张素II生成酶，在心血管组织中很重要。最近，我们开发了一种新型的糜酶特异性抑制性RNA适体HA28，并评估了HA28对心肌功能的影响以及心肌梗死后的死亡率。心肌梗死后用HA28治疗可显着改善超声心动图参数，例如左心室射血分数，分数缩短以及早晚室速的比率。HA28治疗组的死亡率显着降低。媒介物治疗的心肌梗塞组的心脏糜酶活性和糜酶基因表达显着升高，而在HA28治疗的心肌梗塞组中这些显着抑制。本研究提供了第一个证据，即作为一种糜酶特异性抑制剂的单链RNA适体在治疗由心肌梗塞引起的急性心力衰竭中非常有效。胸苷酶可能是心肌梗死后病理生理的新治疗靶点。