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: ECM proteins are instrumental for angiogenesis, which plays momentous roles during development and repair in various organs, including post cardiac insult. After a screening based on an open access RNA-seq database, we identified Nephronectin (NPNT), an extracellular protein, might be involved in cardiac repair post myocardial infarction (MI). However, the specific impact of nephronectin during cardiac repair in MI remains elusive. : In the present study, we established a system overexpressing NPNT locally in mouse heart by utilizing a recombinant adeno-associated virus. One-to-four weeks post MI induction, we observed improved cardiac function, limited infarct size, alleviated cardiac fibrosis, with promoted angiogenesis in infarct border zone in NPNT overexpressed mice. And NPNT treatment enhanced human umbilical vascular endothelial cell (HUVEC) migration and tube formation, putatively through advocating phosphorylation of EGFR/JAK2/STAT3. The migration and capillary-like tube formation events could be readily revoked by EGFR or STAT3 inhibition. Notably, phosphorylation of EGFR, JAK2 and STAT3 were markedly upregulated in AAV2/9-cTnT-NPNT-treated mice with MI. : Our study thus identifies the beneficial effects of NPNT on angiogenesis and cardiac repair post MI by enhancing the EGFR/JAK2/STAT3 signaling pathway, implying the potential therapeutic application of NPNT on myocardial dysfunction post MI.

细胞外基质蛋白在血管生成中起着重要作用，在包括心脏损伤后的各种器官的发育和修复中都发挥着重要作用。在基于开放获取 RNA-seq 数据库的筛选后，我们发现细胞外基质蛋白 Nephrontin（NPNT）可能参与心肌梗死后的心脏修复。然而，NPNT 在心肌梗死后心脏修复中的具体作用仍不清楚。

在本研究中，我们通过利用重组腺相关病毒在小鼠心脏中局部过表达 NPNT。在 MI 诱导后 1 到 4 周，我们观察到 NPNT 过表达小鼠的心脏功能得到改善，梗死面积减小，心脏纤维化减轻，梗死边缘区的血管生成增加。NPNT 处理可增强人脐静脉内皮细胞（HUVEC）的迁移和管状结构形成，推测是通过促进 EGFR/JAK2/STAT3 的磷酸化。EGFR 或 STAT3 的抑制可轻易逆转迁移和毛细血管样管形成事件。值得注意的是，在 MI 后接受 AAV2/9-cTnT-NPNT 治疗的小鼠中，EGFR、JAK2 和 STAT3 的磷酸化明显上调。

我们的研究因此确定了 NPNT 通过增强 EGFR/JAK2/STAT3 信号通路对 MI 后血管生成和心脏修复的有益作用，暗示了 NPNT 在 MI 后心肌功能障碍中的潜在治疗应用。