Department of Oncology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, No. 621, Gangwan Road, Huangpu District, Guangzhou, 510530, China.
Reproductive Medical Center, Affiliated Guangzhou Women and Children's Medical Center of Guangzhou Medical University, No. 9, Jinsui Road, Guangzhou, 510530, China.
Mol Med. 2022 Dec 12;28(1):151. doi: 10.1186/s10020-022-00582-6.
Endometriosis (EMS) is a "tumour-like" gynaecological disease with distant metastasis, and studies have shown that EMS can induce distant metastasis through vascular vessels, but the driving factors and their mechanism are not clear.
We used an EMS animal model and gene knockout technique to explore the role of EMS-induced angiogenesis in EMS metastasis in vivo and in vitro and clarify the role and molecular mechanism of oxLDL in promoting EMS-induced angiogenesis.
We found that microvascular density (MVD) in metastasized ectopic endometrium and eutopic endometrial tissue was higher than that in normal endometrial tissue, and plasma oxLDL was positively correlated with the distant metastasis of EMS. Furthermore, we clarified that oxLDL enhanced the MVD of endometrial tissue by increasing VEGF-A expression and secretion in endometrial cells. Finally, we illustrated the mechanism by which oxLDL promotes VEGF-A expression through the AKT-HIF-1α signalling pathway.
OxLDL is a risk factor promoting distant EMS metastasis by increasing VEGF-A expression and secretion through AKT-HIF-1α signalling. This finding may provide theoretical support and therapeutic targets for the clinical prevention and treatment of EMS.
子宫内膜异位症（EMS）是一种具有远处转移的“肿瘤样”妇科疾病，研究表明 EMS 可以通过血管诱导远处转移，但驱动因素及其机制尚不清楚。
我们使用 EMS 动物模型和基因敲除技术，在体内和体外探索 EMS 诱导的血管生成在 EMS 转移中的作用，并阐明 oxLDL 在促进 EMS 诱导的血管生成中的作用和分子机制。
我们发现转移异位子宫内膜和在位子宫内膜组织中的微血管密度（MVD）高于正常子宫内膜组织，并且血浆 oxLDL 与 EMS 的远处转移呈正相关。此外，我们阐明了 oxLDL 通过增加子宫内膜细胞中 VEGF-A 的表达和分泌来增强子宫内膜组织的 MVD。最后，我们通过 AKT-HIF-1α 信号通路说明了 oxLDL 促进 VEGF-A 表达的机制。
oxLDL 通过 AKT-HIF-1α 信号通路增加 VEGF-A 的表达和分泌，是促进 EMS 远处转移的风险因素。这一发现可能为 EMS 的临床预防和治疗提供理论支持和治疗靶点。
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