Phosphatase and tensin homolog (PTEN) is known to be involved in the pathogenesis of intracranial aneurysm (IA). This study investigated the molecular mechanism of exosomal miR-144-5p (ex-miR-144-5p) and PTEN in IA. Ex-miR-144-5p expression was assessed in serum from individuals with ruptured intracranial aneurysm (RA) or unruptured intracranial aneurysm (UA), and healthy controls (HC). Vascular endothelial cells (VECs) were co-cultured with exosomes isolated from mesenchymal stem cells (MSCs) with transfection of miR-144-5p mimic or miR-144-5p inhibitor. IA rats were induced by combing systemic hypertension and intrathecal elastase injection. VECs were transfected with miR-144-5p mimic or inhibitor to verify the impacts of miR-144-5p on cell viability and proliferation. The connection between miR-144-5p and PTEN was verified by luciferase activity assay. Our data proved that ex-miR-144-5p was decreased in both UA and RA patients. MiR-144-5p overexpression in MSCs-derived exosome promoted VEC viability, inhibited VEC proliferation of VEs, and decreased the protein levels of matrix metalloproteinase-9 (MMP-9), proliferating cell nuclear antigen (PCNA) and osteopontin (OPN). IA rats injected with ex-miR-144-5p mimic showed significant luminal dilation, declined smooth muscle layers, and thinned vascular wall. Besides, inhibited cell apoptosis and decreased protein expressions were also observed. However, ex-miR-144-5p inhibitor had the opposite effects both in vivo and in vitro. We validated that miR-144-5p directly targeted PTEN. MiR-144-5p mimic increased cell viability and proliferation and reduced protein expressions, which could be blunted by PTEN overexpression. This study suggests that miR-144-5p elevates PTEN expression, thereby boosting apoptosis and attenuating viability of VECs in IA.

已知磷酸酶和张力蛋白同源物 (PTEN) 参与颅内动脉瘤 (IA) 的发病机制。本研究探讨了外泌体 miR-144-5p（ex-miR-144-5p）和 PTEN 在 IA 中的分子机制。Ex-miR-144-5p 表达在来自颅内动脉瘤破裂 (RA) 或未破裂颅内动脉瘤 (UA) 的个体和健康对照 (HC) 的血清中进行评估。血管内皮细胞 (VEC) 与从间充质干细胞 (MSC) 分离的外泌体共培养，转染 miR-144-5p 模拟物或 miR-144-5p 抑制剂。通过结合全身性高血压和鞘内注射弹性蛋白酶来诱导IA大鼠。用 miR-144-5p 模拟物或抑制剂转染 VEC，以验证 miR-144-5p 对细胞活力和增殖的影响。miR-144-5p 和 PTEN 之间的联系通过荧光素酶活性测定来验证。我们的数据证明，在 UA 和 RA 患者中，ex-miR-144-5p 均降低。MiR-144-5p在MSCs衍生的外泌体中过表达促进了VEC活力，抑制了VEs的VEC增殖，并降低了基质金属蛋白酶9（MMP-9）、增殖细胞核抗原（PCNA）和骨桥蛋白（OPN）的蛋白质水平。注射了 ex-miR-144-5p 模拟物的 IA 大鼠显示出显着的管腔扩张、平滑肌层下降和血管壁变薄。此外，还观察到细胞凋亡受到抑制和蛋白质表达降低。然而，ex-miR-144-5p 抑制剂在体内和体外均具有相反的作用。我们验证了 miR-144-5p 直接靶向 PTEN。MiR-144-5p 模拟物增加了细胞活力和增殖并降低了蛋白质表达，这可能会被 PTEN 过表达减弱。该研究表明，miR-144-5p 可提高 PTEN 表达，从而促进 IA 中 VEC 的凋亡并减弱其活力。