Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China; Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, 430030, Hubei, China.
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Eur J Pharmacol. 2023 Aug 5;952:175789. doi: 10.1016/j.ejphar.2023.175789. Epub 2023 May 25.
Thoracic aortic dissection (TAD) is common but lethal cardiovascular disease with high mortality. This study aimed to expound whether and how sGC-PRKG1 signaling pathway might promote the formation of TAD. Our work identified two modules with high relevance to TAD using WGCNA method. Combined with previous studies, we focused on the participation of endothelial NOS (eNOS) in the progression of TAD. Through immunohistochemistry, immunofluorescence and western blot we verified that eNOS expression was elevated in the tissues of patients and mice with aortic dissection, and the phosphorylation Ser1177 of eNOS was activated. In a BAPN-induced TAD mouse model, sGC-PRKG1 signaling pathway promotes TAD formation by inducing vascular smooth muscle cells (VSMCs) phenotype transition, which was demonstrated as a decrease in markers of the contractile phenotype of VSMCs such as αSMA, SM22α, and Calponin. These results were also verified by experiments in vitro. To explore the further mechanism, we conducted immunohistochemistry, western blot and quantitative RT-PCR (qPCR), the results of which indicated that sGC-PRKG1 signaling pathway was activated when TAD occurred. In conclusion, our current study revealed that sGC-PRKG1 signaling pathway could promote TAD formation by accelerating VSMCs phenotype switch.
胸主动脉夹层（TAD）是一种常见但致命的心血管疾病，死亡率很高。本研究旨在阐述可溶性鸟苷酸环化酶-PKG1 信号通路是否以及如何促进 TAD 的形成。我们使用 WGCNA 方法确定了与 TAD 高度相关的两个模块。结合以前的研究，我们专注于内皮型一氧化氮合酶（eNOS）在 TAD 进展中的参与。通过免疫组织化学、免疫荧光和 Western blot，我们验证了 eNOS 在主动脉夹层患者和小鼠组织中的表达上调，并且 eNOS 的丝氨酸 1177 磷酸化被激活。在 BAPN 诱导的 TAD 小鼠模型中，sGC-PRKG1 信号通路通过诱导血管平滑肌细胞（VSMCs）表型转变来促进 TAD 的形成，这表现为 VSMCs 的收缩表型标志物如αSMA、SM22α 和 Calponin 的减少。这些结果在体外实验中也得到了验证。为了探索进一步的机制，我们进行了免疫组织化学、Western blot 和定量 RT-PCR（qPCR），结果表明 TAD 发生时 sGC-PRKG1 信号通路被激活。总之，我们目前的研究表明，sGC-PRKG1 信号通路可以通过加速 VSMCs 表型转换来促进 TAD 的形成。
