Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guangxi Key Laboratory Base of Precision Medicine in Cardiocerebrovascular Diseases Control and Prevention, Nanning, China.
Ann Med. 2023;55(2):2237690. doi: 10.1080/07853890.2023.2237690.
Treatment with c-kit-positive cardiac cells (CPCs) has been shown to improve the prognosis of ischemic heart disease. MicroRNAs (miRNAs) confer protection by enhancing the cardiac repair process, but their specific functional mechanisms remain unclear. This study aimed to screen for differentially expressed miRNAs in CPCs under hypoxia and explore their effects on the function of CPCs. We harvested CPCs from C57 adult mice and later performed a high-throughput miRNA sequencing for differential expression profiling analysis. Subsequently, we intervened with the differentially expressed gene miR-210-3p in CPCs and detected changes in the secretion of angiogenesis-related factors through a protein-chip analysis. Finally, we applied CPC supernatants of different groups as conditioned medium to treat mouse cardiac microvascular endothelial cells (CMECs) and further investigated the functional effects of miR-210-3p on c-kit+CPCs under ischemia and hypoxia conditions. The miR-210-3p was highly increased in hypoxia-treated CPCs. Protein-chip detection revealed that CPCs expressed cytokines such as FGF basic, angiogenin, and vascular endothelial growth factor (VEGF) and that hypoxia enhanced their release. Silencing miR-210-3p resulted in a reduction in the release of these angiogenesis-related factors. In addition, the conditioned medium of hypoxia-treated CPCs promoted the proliferation, migration, and tube-forming capabilities of CMECs. In contrast, the conditioned media of CPCs with silenced miR-210-3p after hypoxia decreased the proliferation, migration, and tube-forming ability of CMEC. The CPCs exert proangiogenic effects via paracrine pathways mediated by miR-210-3p. Upregulation of miR-210-3p in hypoxia-treated CPCs may enhance their paracrine function by regulating the secretion of angiogenic factors, thereby promoting angiogenesis in ischemic heart disease.
用 c-kit 阳性心肌细胞（CPCs）治疗已被证明可以改善缺血性心脏病的预后。微小 RNA（miRNAs）通过增强心脏修复过程来提供保护，但它们的具体功能机制尚不清楚。本研究旨在筛选缺氧条件下 CPCs 中差异表达的 miRNAs，并探讨它们对 CPCs 功能的影响。我们从 C57 成年小鼠中收获 CPCs，然后进行高通量 miRNA 测序进行差异表达谱分析。随后，我们用 miR-210-3p 处理 CPCs，并通过蛋白质芯片分析检测血管生成相关因子分泌的变化。最后，我们用不同组别的 CPC 上清液作为条件培养基来处理小鼠心脏微血管内皮细胞（CMECs），并进一步研究 miR-210-3p 在缺血和缺氧条件下对 c-kit+CPCs 的功能影响。miR-210-3p 在缺氧处理的 CPCs 中高度增加。蛋白质芯片检测显示 CPCs 表达了 FGF 基础、血管生成素和血管内皮生长因子（VEGF）等细胞因子，并且缺氧增强了它们的释放。沉默 miR-210-3p 导致这些血管生成相关因子的释放减少。此外，缺氧处理的 CPCs 的条件培养基促进了 CMECs 的增殖、迁移和管状形成能力。相比之下，沉默 miR-210-3p 后的缺氧 CPCs 的条件培养基降低了 CMECs 的增殖、迁移和管状形成能力。CPCs 通过 miR-210-3p 介导的旁分泌途径发挥促血管生成作用。缺氧处理的 CPCs 中 miR-210-3p 的上调可能通过调节血管生成因子的分泌来增强其旁分泌功能，从而促进缺血性心脏病中的血管生成。
