microRNAs (miRNAs) are of importance to chronic heart failure (CHF). However, the relevance of the exosomal miRNAs produced during CHF remains unknown. Our purpose here was to examine the relevance of exosomal microRNA-1246 (miR-1246) released from human umbilical cord mesenchymal stem cell (hucMSC) during CHF and the mechanism of action. Cardiac function, myocardial infarction area, apoptosis, and angiogenesis were all evaluated in a CHF rat model following treatment with hucMSC-derived exosomes (hucMSC-Exos). H9C2 and human umbilical vascular endothelial cells (HUVECs) were subjected to oxygen and glucose deprivation and exosome treatment to quantify the cell proliferation and apoptosis in H9C2 cells and the tube formation capacity of the HUVECs. A dual-luciferase activity reporter assay was conducted to validate the interaction between miR-1246 and serine protease 23 (PRSS23). HucMSCs treatment led to a reduction in H9C2 apoptosis and an increase in HUVEC angiogenesis, which were mitigated when hucMSCs were treated with a miR-1246 inhibitor. We also confirmed that PRSS23 is a putative target of miR-1246 and that miR-1246 attenuated hypoxia-induced myocardial tissue damage by targeting PRSS23 and inhibiting the activation of the Snail/alpha-smooth muscle actin signaling. Our findings suggest that exosomal miR-1246 from hucMSCs protects the heart from failure by targeting PRSS23.

中文翻译：

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来自人脐带间充质干细胞的外泌体 microRNA-1246 可增强慢性心力衰竭中的心肌血管生成

microRNA (miRNA) 对慢性心力衰竭 (CHF) 很重要。然而，在 CHF 期间产生的外泌体 miRNA 的相关性仍然未知。我们的目的是检查在 CHF 期间从人脐带间充质干细胞 (hucMSC) 释放的外泌体 microRNA-1246 (miR-1246) 的相关性及其作用机制。在用 hucMSC 衍生的外泌体 (hucMSC-Exos) 治疗后，在 CHF 大鼠模型中评估了心脏功能、心肌梗死面积、细胞凋亡和血管生成。对 H9C2 和人脐血管内皮细胞 (HUVECs) 进行氧和葡萄糖剥夺和外泌体处理，以量化 H9C2 细胞中的细胞增殖和凋亡以及 HUVECs 的管形成能力。进行双荧光素酶活性报告基因测定以验证 miR-1246 和丝氨酸蛋白酶 23 (PRSS23) 之间的相互作用。HucMSCs 治疗导致 H9C2 细胞凋亡减少和 HUVEC 血管生成增加，当用 miR-1246 抑制剂处理 hucMSCs 时，这种情况得到缓解。我们还证实 PRSS23 是 miR-1246 的推定靶标，并且 miR-1246 通过靶向 PRSS23 并抑制 Snail/α-平滑肌肌动蛋白信号传导的激活来减轻缺氧诱导的心肌组织损伤。我们的研究结果表明，来自 hucMSCs 的外泌体 miR-1246 通过靶向 PRSS23 保护心脏免于衰竭。我们还证实 PRSS23 是 miR-1246 的推定靶标，并且 miR-1246 通过靶向 PRSS23 并抑制 Snail/α-平滑肌肌动蛋白信号传导的激活来减轻缺氧诱导的心肌组织损伤。我们的研究结果表明，来自 hucMSCs 的外泌体 miR-1246 通过靶向 PRSS23 保护心脏免于衰竭。我们还证实 PRSS23 是 miR-1246 的推定靶标，并且 miR-1246 通过靶向 PRSS23 并抑制 Snail/α-平滑肌肌动蛋白信号传导的激活来减轻缺氧诱导的心肌组织损伤。我们的研究结果表明，来自 hucMSCs 的外泌体 miR-1246 通过靶向 PRSS23 保护心脏免于衰竭。