Li Chunyu, Zheng Chongming, Pu Yanan, Zhou Haoyang, Li Ying, Wang Weiwei, Chen Xufeng, Zhang Cheng, Chen Yan
Department of Emergency and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Emergency and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Emergency and Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215000, China.
Cell Signal. 2025 Jan;125:111512. doi: 10.1016/j.cellsig.2024.111512. Epub 2024 Nov 16.
Reversing cardiac fibrosis contributes to the restoration of cardiac function in acute myocardial infarction (MI). Exosomes-derived mesenchymal stem cells (MSCs) have been established as potential biomarkers of cardiovascular diseases. While vericiguat has demonstrated promising outcomes in MI via reverse hypertrophy and fibrosis, previous studies about vericiguat pretreatment with MSCs is limited. We aim at exploring whether exosomes derived from vericiguat pretreatment MSCs could augment cardioprotective function and the underlying mechanisms. In our study, exosomes isolated from MSCs (MSC-Exo) and pretreated with vericiguat (MSC-Exo) were administered to cardiac fibroblasts (CFs) in vitro and male infarcted Sprague-Dawley rat hearts in vivo. In vivo, MSC-Exo could significantly improve cardiac function and attenuate cardiac fibrosis and decrease the expression of α-smooth muscle actin (α-SMA), Ι and III collagen (Col Ι and Col III) compared to MSC-Exo treatment. In vitro, MSC-Exo could also restrain proliferation, migration, and the profibrotic genes expression in CFs. miR-1180-3p was enrich in MSC-Exo. Besides, miR-1180-3p could be delivered to CFs via Exo and alleviated TGF-β1-induced fibrosis through inhibiting ETS1 signaling. The elucidation of this mechanism suggested that exosomes derived from vericiguat pretreatment MSCs could improve cardioprotective effects through promoting CFs function. MiR-1180-3p targeting ETS1 played an important role in antifibrosis.
逆转心脏纤维化有助于急性心肌梗死（MI）患者心脏功能的恢复。间充质干细胞（MSC）来源的外泌体已被确立为心血管疾病的潜在生物标志物。虽然维立西呱已通过逆转心肌肥厚和纤维化在心肌梗死中显示出有前景的结果，但之前关于维立西呱预处理间充质干细胞的研究有限。我们旨在探索维立西呱预处理间充质干细胞来源的外泌体是否能增强心脏保护功能及其潜在机制。在我们的研究中，从间充质干细胞分离的外泌体（MSC-Exo）并用维立西呱预处理（Ver-MSC-Exo），在体外给予心脏成纤维细胞（CFs），在体内给予雄性梗死的Sprague-Dawley大鼠心脏。在体内，与MSC-Exo处理相比，Ver-MSC-Exo可显著改善心脏功能，减轻心脏纤维化，并降低α-平滑肌肌动蛋白（α-SMA）、Ⅰ型和Ⅲ型胶原蛋白（ColⅠ和ColⅢ）的表达。在体外，Ver-MSC-Exo还可抑制CFs的增殖、迁移和促纤维化基因表达。miR-1180-3p在Ver-MSC-Exo中富集。此外，miR-1180-3p可通过外泌体传递至CFs，并通过抑制ETS1信号减轻TGF-β1诱导的纤维化。该机制的阐明表明，维立西呱预处理间充质干细胞来源的外泌体可通过促进CFs功能改善心脏保护作用。靶向ETS1的miR-1180-3p在抗纤维化中起重要作用。
