AHR canonical pathway: in vivo findings to support novel antihypertensive strategies
AHR canonical pathway: in vivo findings to support novel antihypertensive strategies
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DOI：
10.1016/j.phrs.2020.105407
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发表时间：
2021-03-16
影响因子：
9.3
通讯作者：
Monteiro, Emilia C.
中科院分区：
文献类型：
--
作者：
Coelho, Nuno R.;Matos, Clara;Monteiro, Emilia C.
原发性高血压（HTN）是一种遗传和环境因素相互作用产生一组几乎无法区分的高流行表型的疾病。由于缺乏对环境-基因相互作用及其对血压（BP）的影响和机制的了解，对HTN保护伞下的内容定义不明确。这些感觉和（异常）适应有毒环境刺激的机制的揭示可能至少决定了一些基本HTN的表型，并将具有重要的治疗意义。在本文中，我们更接近于环境传感器芳烃受体（AHR），这是一种参与心血管生理学的配体激活转录因子，但它通过其典型途径参与异种生物转化而为人所知。本综述旨在揭示ahr -规范通路对HTN的贡献。为了更好地反映BP调节机制的复杂性，我们从体内研究中获得了证据。在这里，我们确定了现有证据的水平和HTN的ahr相关表型的综合表征。我们回顾了AHR- htn基因关联、AHR配体及其对血压影响的临床和啮齿动物研究。我们得出结论，AHR是HTN环境暴露的可药物机制联系。我们的结论是，研究AHR的典型途径及其相关基因和/或其他生物标志物（如色氨酸相关配体）的表达/多态性是值得的，以便确定可能从AHR为中心的降压治疗中获益的患者。
Essential hypertension (HTN) is a disease where genetic and environmental factors interact to produce a high prevalent set of almost indistinguishable phenotypes. The weak definition of what is under the umbrella of HTN is a consequence of the lack of knowledge on the players involved in environment-gene interaction and their impact on blood pressure (BP) and mechanisms. The disclosure of these mechanisms that sense and (mal)adapt to toxic-environmental stimuli might at least determine some phenotypes of essential HTN and will have important therapeutic implications. In the present manuscript, we looked closer to the environmental sensor aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor involved in cardiovascular physiology, but better known by its involvement in biotransformation of xenobiotics through its canonical pathway. This review aims to disclose the contribution of the AHR-canonical pathway to HTN. For better mirror the complexity of the mechanisms involved in BP regulation, we privileged evidence from in vivo studies. Here we ascertained the level of available evidence and a comprehensive characterization of the AHR-related phenotype of HTN. We reviewed clinical and rodent studies on AHR-HTN genetic association and on AHR ligands and their impact on BP. We concluded that AHR is a druggable mechanistic linker of environmental exposure to HTN. We conclude that is worth to investigate the canonical pathway of AHR and the expression/polymorphisms of its related genes and/or other biomarkers (e.g. tryptophan-related ligands), in order to identify patients that may benefit from an AHR-centered antihypertensive treatment.