Rationale: An increase of severe ischemic heart diseases results in an increase of the patients with congestive heart failure (CHF). Therefore, new therapies are expected in addition to recanalization of coronary arteries. Previous clinical trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs.

Objective: We aimed at investigating whether OSTN (osteocrin) peptide potentially functioning as an NPR (NP clearance receptor) 3-blocking peptide can be used as a new therapeutic peptide for treating CHF after myocardial infarction (MI) using animal models.

Methods and Results: We examined the effect of OSTN on circulation using 2 mouse models; the continuous intravenous infusion of OSTN after MI and the OSTN-transgenic (Tg) mice with MI. In vitro studies revealed that OSTN competitively bound to NPR3 with atrial NP. In both OSTN–continuous intravenous infusion model and OSTN-Tg model, acute inflammation within the first week after MI was reduced. Moreover, both models showed the improvement of prognosis at 28 days after MI by OSTN. Consistent with the in vitro study binding of OSTN to NPR3, the OSTN-Tg exhibited an increased plasma atrial NP and C-type NP, which might result in the improvement of CHF after MI as indicated by the reduced weight of hearts and lungs and by the reduced fibrosis.

Conclusions: OSTN might suppress the worsening of CHF after MI by inhibiting clearance of NP family peptides.

中文翻译：

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利钠肽家族的新分泌肽Osteocrin抑制心肌梗死后的充血性心力衰竭进展及其新颖性和意义

理由：严重的缺血性心脏病的增加导致充血性心力衰竭（CHF）患者的增加。因此，除了冠状动脉再通之外，还期望有新的疗法。先前使用利钠肽（NP）的临床试验证明NP可改善CHF。

目的：我们旨在使用动物模型研究可能用作NPR（NP清除受体）3阻断肽的OSTN（osteocrin）肽是否可作为治疗心肌梗死（MI）后CHF的新型治疗肽。

方法和结果：我们使用2种小鼠模型检查了OSTN对循环的影响。在MI和OSTN转基因（Tg）小鼠中注入MI后，连续静脉输注OSTN。体外研究显示OSTN与心房NP竞争性结合NPR3。在OSTN连续静脉输注模型和OSTN-Tg模型中，MI发生后第一周内的急性炎症均得到减轻。此外，两种模型均显示OSTN导致心梗后28天的预后有所改善。与OSTN与NPR3的体外研究结合相一致，OSTN-Tg的血浆心房NP和C型NP升高，这可能导致MI后CHF改善，如心脏和肺部重量的减少以及减少纤维化。

结论： OSTN可能通过抑制NP家族肽的清除而抑制MI后CHF的恶化。