Zhang Jimei, Zhang Chonghong, Miao Li, Meng Zimin, Gu Ning, Song Guifang
Department of Material Supply, Yantai Yuhuangding Hospital, Yantai, Shandong, China.
Department of Material Purchasing, Yantai Yeda Hospital, China.
Arch Med Sci. 2021 Jul 3;20(4):1197-1208. doi: 10.5114/aoms/139235. eCollection 2024.
Ox-LDL (oxidized low-density lipoprotein)-induced endothelial cell injury and dysfunction of vascular smooth muscle cells play critical roles in the development of atherosclerosis (AS). Tropomyosin 2 (TPM2) has been implicated in cardiac diseases, but its critical role and regulatory mechanism in AS progression have not yet been elucidated.
The expression of TPM2 was investigated in AS tissues. Ox-LDL was used to construct an AS model based on endothelial and vascular smooth muscle cells (HAECs and VSMCs). An overexpression assay was performed to evaluate the role of TPM2 in AS. Meanwhile, the involvement of the RhoA pathway in TPM2-mediated AS progression was evaluated using narciclasine.
Tropomyosin 2 was dramatically upregulated in both AS tissues and ox-LDL-induced HAECs. Overexpression of TPM2 attenuated ox-LDL-stimulated cell growth depression, inflammatory and adhesive responses in HAECs, as well as oxidative stress and mitochondrial dysfunction. Additionally, VSMCs, impacted by TPM2-overexpressed HAECs, showed alleviated cellular processes which were abnormally activated by ox-LDL. Furthermore, depressed activation of the RhoA pathway was found in TPM2-overexpressed HAECs and activating the signaling rescued these effects of TPM2 exerted on ox-LDL-stimulated HAECs and VSMCs.
TPM2 had an advantageous impact on ox-LDL-induced AS progression by mediating the RhoA pathway. This evidence might contribute to the therapy of AS.
氧化型低密度脂蛋白（Ox-LDL）诱导的内皮细胞损伤和血管平滑肌细胞功能障碍在动脉粥样硬化（AS）的发展中起关键作用。原肌球蛋白2（TPM2）与心脏疾病有关，但其在AS进展中的关键作用和调控机制尚未阐明。
研究TPM2在AS组织中的表达。使用Ox-LDL构建基于内皮细胞和血管平滑肌细胞（人主动脉内皮细胞和血管平滑肌细胞）的AS模型。进行过表达实验以评估TPM2在AS中的作用。同时，使用水仙环素评估RhoA途径在TPM2介导的AS进展中的参与情况。
原肌球蛋白2在AS组织和Ox-LDL诱导的人主动脉内皮细胞中均显著上调。TPM2的过表达减轻了Ox-LDL刺激的人主动脉内皮细胞的细胞生长抑制、炎症和黏附反应，以及氧化应激和线粒体功能障碍。此外，受TPM2过表达的人主动脉内皮细胞影响的血管平滑肌细胞显示出由Ox-LDL异常激活的细胞过程得到缓解。此外，在TPM2过表达的人主动脉内皮细胞中发现RhoA途径的激活受到抑制，激活该信号通路可挽救TPM2对Ox-LDL刺激的人主动脉内皮细胞和平滑肌细胞产生的这些影响。
TPM2通过介导RhoA途径对Ox-LDL诱导的AS进展具有有利影响。这一证据可能有助于AS的治疗。
