From the Department of Cell Biology (T.M., A.C., H.T.-W., H.I., K.S., H.F., N. Mochizuki), Department of Regenerative Medicine and Tissue Engineering (K.O.), Department of Biochemistry (H.N., T.T.), Omics Research Center, National Cerebral and Cardiovascular Center Research Institute (A.M., N. Minamino), Department of Diabetes, Endocrinology, and Nutrition, Graduate School of Medicine, Kyoto University, Japan (Y.K., A.Y.); Center for Cerebral and Cardiovascular Disease Information, National Cerebral and Cardiovascular Center, Suita, Japan (S.O., K.N.); and AMED-CREST, Suita, Japan (N. Mochizuki).
Circ Res. 2018 Mar 2;122(5):742-751. doi: 10.1161/CIRCRESAHA.117.312624. Epub 2018 Jan 11.
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.
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.
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.
OSTN might suppress the worsening of CHF after MI by inhibiting clearance of NP family peptides.
严重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，还需要新的治疗方法。以前使用利钠肽（NPs）的临床试验证明了 NPs 改善 CHF 的作用。
我们旨在研究骨钙素（Osteocrin）肽作为一种潜在的 NPR（NP 清除受体）3 阻断肽，是否可以在心肌梗死后（MI）的动物模型中用作治疗 CHF 的新治疗肽。
我们使用 2 种小鼠模型研究了 OSTN 对循环的影响；MI 后 OSTN 的连续静脉输注和具有 MI 的 OSTN 转基因（Tg）小鼠。体外研究表明，OSTN 与心房 NP 竞争结合 NPR3。在 OSTN 持续静脉输注模型和 OSTN-Tg 模型中，MI 后第一周内的急性炎症均减少。此外，OSTN 可改善 MI 后 28 天的预后。与体外研究中 OSTN 与 NPR3 的结合一致，OSTN-Tg 表现出增加的血浆心房 NP 和 C 型 NP，这可能导致 MI 后 CHF 的改善，如心脏和肺的重量减轻以及纤维化减少所表明的那样。
OSTN 可能通过抑制 NP 家族肽的清除来抑制 MI 后 CHF 的恶化。
