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血管内皮生长因子受体1、血管内皮生长因子受体2、血管内皮生长因子受体3、促凋亡蛋白BAX和抗凋亡蛋白BCL-2在静脉曲张发病机制中的关键作用:揭示分子机制

Critical Roles of VEGFR1, VEGFR2, VEGFR3, BAX, and BCL-2 in the Pathogenesis of Varicose Veins: Unveiling Molecular Mechanisms.

作者信息

Abedinzadeh Mehdi, Nazari Alireza, Vahidi Seraj-Aldin, Pourmasumi Soheila, Khorramdelazad Hossein

机构信息

Department of Urology, Shahid Rahnemoon Hospital, Shahid Sadoughi University of Medical Sciences and Health Service, Yazd, Iran.

Social Determinants of Health Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Am J Mens Health. 2025 Mar-Apr;19(2):15579883251321588. doi: 10.1177/15579883251321588. Epub 2025 Mar 13.

DOI:10.1177/15579883251321588
PMID:40079569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11907509/
Abstract

Varicocele is characterized by the abnormal dilation of veins within the testicular pampiniform plexus, contributing to inflammation, pain, and infertility in males. The precise roles of vascular endothelial growth factor receptors (VEGFRs), B-cell lymphoma 2 (BCL-2), and BCL-2-associated X-protein (BAX) in the pathology of varicocele still need to be clarified. This study sought to investigate the protein expression levels of VEGFR1, VEGFR2, VEGFR3, BCL-2, and BAX in varicose and healthy vessels from patients diagnosed with varicocele. Tissue samples were collected from 20 varicose veins and 20 healthy vessels from patients diagnosed with varicocele. Western blotting was utilized to quantify VEGFR1, VEGFR2, VEGFR3, BCL-2, and BAX protein levels. Analysis revealed a statistically significant increase in VEGFR3 protein expression within varicose veins compared to healthy vessels ( = .0473), while no significant differences were observed in the levels of VEGFR1 and VEGFR2 between the two groups. Concerning apoptotic signaling proteins, no significant differences were noted in the individual expression levels of BAX and BCL-2; however, the BAX/BCL-2 ratio was approximately 1.29 in varicose vessels. This ratio, exceeding 1.0, may suggest a pro-apoptotic shift in varicose veins and indicates a potential involvement of apoptosis in the pathology of varicocele. These findings suggest that VEGFR3 may play a pivotal role in the pathogenesis of varicocele and could contribute to vascular alterations associated with this condition. Furthermore, the elevated BAX/BCL-2 ratio implies a pro-apoptotic environment within varicose veins, thereby implicating apoptosis as a possible mechanism in the development of varicocele. Further exploration of VEGFR3-related signaling pathways and apoptotic markers may yield valuable insights for identifying therapeutic targets in managing varicocele.

摘要

精索静脉曲张的特征是睾丸蔓状静脉丛内静脉异常扩张,可导致男性炎症、疼痛和不育。血管内皮生长因子受体(VEGFRs)、B细胞淋巴瘤2(BCL-2)和BCL-2相关X蛋白(BAX)在精索静脉曲张病理中的具体作用仍有待阐明。本研究旨在调查诊断为精索静脉曲张患者的曲张静脉和健康血管中VEGFR1、VEGFR2、VEGFR3、BCL-2和BAX的蛋白表达水平。从诊断为精索静脉曲张的患者的20条曲张静脉和20条健康血管中采集组织样本。采用蛋白质印迹法对VEGFR1、VEGFR2、VEGFR3、BCL-2和BAX蛋白水平进行定量分析。分析显示,与健康血管相比,曲张静脉中VEGFR3蛋白表达有统计学意义的增加(P = 0.0473),而两组间VEGFR1和VEGFR2水平无显著差异。关于凋亡信号蛋白,BAX和BCL-2的个体表达水平无显著差异;然而,曲张血管中BAX/BCL-2比值约为1.29。该比值超过1.0,可能提示曲张静脉中存在促凋亡转变,并表明凋亡可能参与精索静脉曲张的病理过程。这些发现表明,VEGFR3可能在精索静脉曲张的发病机制中起关键作用,并可能导致与该疾病相关的血管改变。此外,升高的BAX/BCL-2比值意味着曲张静脉内存在促凋亡环境,从而暗示凋亡可能是精索静脉曲张发生发展的一种机制。进一步探索VEGFR3相关信号通路和凋亡标志物可能为确定精索静脉曲张治疗靶点提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfc/11907509/97732763ca77/10.1177_15579883251321588-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfc/11907509/03c1e68171a2/10.1177_15579883251321588-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfc/11907509/97732763ca77/10.1177_15579883251321588-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfc/11907509/03c1e68171a2/10.1177_15579883251321588-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfc/11907509/97732763ca77/10.1177_15579883251321588-fig2.jpg

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本文引用的文献

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Insight into inflammation involvement in varicocele: A narrative review.精索静脉曲张中炎症参与的研究进展:一篇综述。
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The Safety of Anti-VEGF Treatment, in the Context of the Retinal Nerve Fibre Layer, in Patients with Wet Age-Related Macular Degeneration: A Review.
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A systematic review and meta-analysis on the efficacy of internal spermatic artery ligation during laparoscopic varicocelectomy in children and adolescents: Is it safe?一项关于在儿童和青少年腹腔镜精索静脉结扎术中结扎精索内动脉的疗效的系统评价和荟萃分析:安全吗?
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