Liu Yi, He Changqing, Zhong Quanhai, Shi Xianbao, Li Hongyan, Fu Gaoge, Guo Lixuan, Zhao Churong, Tian Lei, Li Xin, Jiao Xue, Shan Lina
Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, 121000, People's Republic of China.
Department of Critical Care Medicine, Panzhihua Central Hospital, Panzhihua, 61700, People's Republic of China.
Int J Nanomedicine. 2024 Dec 19;19:13525-13546. doi: 10.2147/IJN.S493047. eCollection 2024.
Pulmonary hypertension (PH) is a progressive and life-threatening condition. Recent research has demonstrated that exosomes derived from mesenchymal stem cells (MSC) exhibit significant therapeutic potential in the treatment of PH. The composition of these exosomes is often substantially influenced by the characteristics of their parental cells. This study aimed to identify an intervention strategy to enhance the efficacy of mesenchymal stem cell exosomes in treating PH.
Exosomes were isolated from control MSC and tadalafil-pretreated MSCs. In vitro and in vivo studies were conducted.
MSC attenuated macrophage inflammation and improved endothelial cell (EC) apoptosis while also reducing pulmonary arterial pressure in a hypoxia-induced rat model. Furthermore, MSC exosomes can mitigate hypoxia-induced proliferation and migration of smooth muscle cells (SMC) by influencing the secretion of endothelial exosomes. MiR-29a-3p has been identified as a crucial mediator in this process, with its expression regulated by cAMP responsive element binding protein 1 (CREB1). MiR-29a-3p exerts anti-inflammatory effects by modulating the expression of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Notably, the anti-inflammatory and anti-vascular remodeling activities of exosomes were diminished following the depletion of MiR-29a-3p.
MSC treated with tadalafil can secrete better exosomes. MSC may enhance anti-inflammatory and anti-vascular remodeling properties by upregulating mir-29a-3p expression, providing a novel idea for PH therapy. Future studies could explore the clinical application of this finding.
肺动脉高压（PH）是一种进行性且危及生命的疾病。最近的研究表明，间充质干细胞（MSC）衍生的外泌体在治疗PH方面具有显著的治疗潜力。这些外泌体的组成通常受到其亲本细胞特征的显著影响。本研究旨在确定一种干预策略，以提高间充质干细胞外泌体治疗PH的疗效。
从对照MSC和他达拉非预处理的MSC中分离外泌体。进行了体外和体内研究。
在缺氧诱导的大鼠模型中，MSC减轻了巨噬细胞炎症，改善了内皮细胞（EC）凋亡，同时还降低了肺动脉压。此外，MSC外泌体可通过影响内皮外泌体的分泌来减轻缺氧诱导的平滑肌细胞（SMC）增殖和迁移。已确定miR-29a-3p是这一过程中的关键介质，其表达受环磷酸腺苷反应元件结合蛋白1（CREB1）调节。miR-29a-3p通过调节外核苷酸焦磷酸酶/磷酸二酯酶2（ENPP2）的表达发挥抗炎作用。值得注意的是，miR-29a-3p缺失后，外泌体的抗炎和抗血管重塑活性减弱。
用他达拉非处理的MSC可以分泌更好的外泌体。MSC可能通过上调mir-29a-3p表达来增强抗炎和抗血管重塑特性，为PH治疗提供了新的思路。未来的研究可以探索这一发现的临床应用。
