Abstract

Aryl hydrocarbon receptor (AhR) is a transcription factor, which can be activated by a plethora of structure-diverse ligands. Historically, AhR is known for its involvements in regulation of metabolism of xenobiotics. However, normal physiological roles of AhR have been defined in other essential biological processes, including vascular growth and function, reproduction, and immunoresponses. In contrast, aberrant expression and activation of the AhR signaling pathway occur in a variety of human diseases, many of which (e.g., preeclampsia, atherosclerosis, and hypertension) could be associated with endothelial dysfunction. Indeed, emerging evidence has shown that either exogenous or endogenous AhR ligands can induce endothelial dysfunction in either an AhR-dependent or AhR-independent manner, possibly reliant on the blood vessel origin (artery and vein) of endothelial cells. Given that the AhR signaling pathway has broad impacts on endothelial and cardiovascular function, AhR ligands, AhR, and their downstream genes could be considered novel therapeutic targets for those endothelial-related diseases. This review will discuss the current knowledge of AhR’s mediation on endothelial function and potential mechanisms underlying these actions with a focus on placental endothelial cells.

中文翻译：

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芳基烃受体在内皮血管生成反应中的作用†。

摘要

芳基烃受体 (AhR) 是一种转录因子，可以被多种结构多样化的配体激活。从历史上看，AhR 因其参与外源物质代谢调节而闻名。然而，AhR 的正常生理作用已在其他重要的生物过程中得到定义，包括血管生长和功能、繁殖和免疫反应。相反，AhR信号通路的异常表达和激活发生在多种人类疾病中，其中许多疾病（例如先兆子痫、动脉粥样硬化和高血压）可能与内皮功能障碍有关。事实上，新出现的证据表明，外源性或内源性 AhR 配体可以以 AhR 依赖性或 AhR 独立性方式诱导内皮功能障碍，可能依赖于内皮细胞的血管起源（动脉和静脉）。鉴于AhR信号通路对内皮和心血管功能具有广泛影响，AhR配体、AhR及其下游基因可被视为内皮相关疾病的新治疗靶点。本综述将讨论 AhR 对内皮功能的调节的最新知识以及这些作用的潜在机制，重点关注胎盘内皮细胞。