Tian Zexiang, Li Wei, Wang Jian, Li Shuzhen
Department of Cardiothoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, No.1, Tongdao North Street, Huimin District, Hohhot, 010050, China.
Gen Thorac Cardiovasc Surg. 2025 Feb 19. doi: 10.1007/s11748-025-02130-5.
Abdominal aortic aneurysm (AAA) is a common aneurysm that is often associated with atherosclerosis and can lead to artery rupture and death. Brain abundant membrane attached signal protein 1 (BASP1) is related to a variety of pathophysiological processes, but its role in AAA has not been reported.
Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to detect the expressions of BASP1 and Wilms' tumor 1-associated protein (WTAP). Angiotensin-II (Ang-II) was employed for inducing AAA models in vitro to explore the effects and mechanism of BASP1 in AAA. Cell viability, apoptosis, oxidative stress level, and Fe level were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and various kits, respectively. In terms of mechanism, the methylated RNA immunoprecipitation (MeRIP)-qPCR, the dual luciferase reporter assay, and the cytochrome experiments were utilized to evaluate the relationship between BASP1 and WTAP.
A highly expressed level of BASP1 was observed in aortic tissues of AAA patients and Ang-II could induce AAA models by treating vascular smooth muscle cells (VSMCs). In cellular function, BASP1 knockdown impaired AAA and ferroptosis resulted from Ang-II. Mechanically, WTAP mediated the N6-methyladenosine (m6A) modification and mRNA stability of BASP1. Meanwhile, WTAP was highly expressed in AAA tissues of patients and the effects of WTAP silence in AAA and ferroptosis were diminished by up-regulated BASP1.
WTAP promotes cell viability and inhibits apoptosis and ferroptosis resulted from Ang-II in VSMCs by mediating the m6A level of BASP1.
腹主动脉瘤（AAA）是一种常见的动脉瘤，常与动脉粥样硬化相关，可导致动脉破裂和死亡。脑丰富膜附着信号蛋白1（BASP1）与多种病理生理过程有关，但其在AAA中的作用尚未见报道。
采用实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测BASP1和肾母细胞瘤1相关蛋白（WTAP）的表达。应用血管紧张素II（Ang-II）体外诱导AAA模型，探讨BASP1在AAA中的作用及机制。分别采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基四氮唑溴盐（MTT）法、流式细胞术和各种试剂盒检测细胞活力、细胞凋亡、氧化应激水平和铁水平。在机制方面，采用甲基化RNA免疫沉淀（MeRIP）-qPCR、双荧光素酶报告基因检测和细胞色素实验评估BASP1与WTAP之间的关系。
在AAA患者的主动脉组织中观察到BASP1的高表达水平，Ang-II可通过处理血管平滑肌细胞（VSMC）诱导AAA模型。在细胞功能方面，BASP1基因敲低可损害AAA，Ang-II可导致铁死亡。机制上，WTAP介导BASP1的N6-甲基腺苷（m6A）修饰和mRNA稳定性。同时，WTAP在患者的AAA组织中高表达，上调BASP1可减弱WTAP沉默对AAA和铁死亡的影响。
WTAP通过介导BASP1的m6A水平促进VSMC的细胞活力，抑制Ang-II诱导的细胞凋亡和铁死亡。
