Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage.

中文翻译：

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MAPKAP激酶2肽抑制剂MMI-0100的雾化递送可预防局部缺血引起的收缩功能障碍。

急性心肌梗塞（AMI）导致收缩功能障碍，心肌炎和纤维化重塑，从而导致心脏不可逆的病理重塑。相关的细胞死亡和炎症引起细胞因子释放，从而激活p38 MAPK信号通路，通过MAPKAP激酶2（MK2）传播破坏性信号。以前我们显示，腹膜内注射MK2的细胞可渗透肽抑制剂MMI-0100，可防止由左前降支冠状动脉（LAD）结扎诱发的AMI小鼠模型的纤维化，凋亡和收缩功能障碍。在这里，我们测试了MMI-0100的新给药途径：雾化肽的吸入。当在AMI的30分钟内给予，并在其后2周每天给予一次时，通过有意识的超声心动图测量，吸入和注射的MMI-0100均可改善心脏功能。两周后通过Massons三色染色观察到有限的纤维化，表明MMI-0100在形成明显的纤维化之前可以保护心脏。这些结果支持MMI-0100的雾化给药途径可以保护心肌免受缺血性损伤。