Zha Binshan, Qiu Peng, Zhang Chenxin, Li Xinyuan, Chen Zhiyong
Department of Vascular and Thyroid Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, and Vascular Center of Shanghai Jiaotong University, Shanghai, People's Republic of China.
Onco Targets Ther. 2020 May 6;13:3801-3808. doi: 10.2147/OTT.S244128. eCollection 2020.
Lower extremity varicose veins (LEVVs) are a common venous disorder of venous dilation and tortuosity. The functional integrity of vascular smooth muscle cells (VSMCs), the majority of the cells in venous tissues, and their phenotypic differences play important roles in the occurrence and development of LEVV. However, the underlying mechanism remains unclear.
The expression of estrogen receptors ERα and ERβ and G-protein-coupled receptor 30 (GPR30) in LEVV tissues and the role of GPR30 in VSMC phenotypic switching were examined by Western blotting and quantitative real-time PCR. Finally, the related mechanisms underlying LEVVs were explored by Western blotting.
The serum estradiol content was increased in LEVV patients compared with normal control patients, but the mRNA levels of ERα and ERβ were not significantly different. GPR30 was overexpressed in LEVVs, and high expression of GPR30 promoted the maintenance of a synthetic phenotype in which OPN, MMP-1 and MMP-9 were highly expressed and α-SMA was poorly expressed in VSMCs. Finally, the mechanism by which GPR30 promotes the phenotypic switching of VSMCs is dependent on the ERK1/2 and AKT pathways.
GPR30 may contribute to the pathogenesis of LEVVs by promoting the maintenance of a synthetic phenotype in VSMCs by activating the ERK1/2 and AKT pathways, and GPR30 might be a novel therapeutic target for clinical LEVV treatment.
下肢静脉曲张（LEVVs）是一种常见的静脉扩张和迂曲的静脉疾病。血管平滑肌细胞（VSMC）是静脉组织中的主要细胞类型，其功能完整性及其表型差异在LEVV的发生和发展中起重要作用。然而，其潜在机制仍不清楚。
通过蛋白质免疫印迹法和定量实时聚合酶链反应检测LEVV组织中雌激素受体ERα和ERβ以及G蛋白偶联受体30（GPR30）的表达，以及GPR30在VSMC表型转换中的作用。最后，通过蛋白质免疫印迹法探讨LEVVs的相关机制。
与正常对照患者相比，LEVV患者血清雌二醇含量升高，但ERα和ERβ的mRNA水平无显著差异。GPR30在LEVVs中过表达，GPR30的高表达促进了VSMC中骨桥蛋白（OPN）、基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶-9（MMP-9）高表达而α-平滑肌肌动蛋白（α-SMA）低表达的合成表型的维持。最后，GPR30促进VSMC表型转换的机制依赖于细胞外信号调节激酶1/2（ERK1/2）和蛋白激酶B（AKT）信号通路。
GPR30可能通过激活ERK1/2和AKT信号通路促进VSMC中合成表型的维持，从而参与LEVVs的发病机制，GPR30可能是临床治疗LEVVs的新靶点。
