Role of the Peroxisome Proliferator Activated Receptors in Hypertension.
Role of the Peroxisome Proliferator Activated Receptors in Hypertension.
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过氧化物酶体增殖物在高血压中活化受体的作用。
DOI：
10.1161/circresaha.120.318062
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发表时间：
2021-04-02
影响因子：
20.1
通讯作者：
Sigmund CD
中科院分区：
文献类型：
--
作者：
Fang S;Livergood MC;Nakagawa P;Wu J;Sigmund CD
核受体是一个由配体激活的转录因子大家庭，它们通过调节基因表达的变化来感知生理环境并进行长期适应。在这篇综述中，我们将首先讨论核受体介导其转录反应的基本机制。我们将重点关注被收养的孤儿受体PPAR家族，特别关注PPARγ，这是最令人信服的证据，是动脉血压的重要调节剂。我们将回顾显示PPARγ罕见突变导致严重高血压的遗传数据和显示PPARγ激活剂对血压有益的临床试验数据。我们将详细介绍脑、肾、血管和免疫系统中的ppar调节血压和相关表型（如内皮功能）的组织和细胞特异性分子机制。最后，我们将讨论胎盘ppar在子痫前期的作用，子痫前期是一种危及生命的妊娠高血压。最后，我们将对未来的研究方向和开发新疗法的意义提出看法。
Nuclear receptors represent a large family of ligand-activated transcription factors which sense the physiological environment and make long-term adaptations by mediating changes in gene expression. In this review, we will first discuss the fundamental mechanisms by which nuclear receptors mediate their transcriptional responses. We will focus on the PPAR family of adopted orphan receptors paying special attention to PPARγ, the isoform with the most compelling evidence as an important regulator of arterial blood pressure. We will review genetic data showing that rare mutations in PPARγ cause severe hypertension and clinical trial data which show that PPARγ activators have beneficial effects on blood pressure. We will detail the tissue- and cell-specific molecular mechanisms by which PPARs in the brain, kidney, vasculature and immune system modulates blood pressure and related phenotypes such as endothelial function. Finally, we will discuss the role of placental PPARs in preeclampsia, a life-threatening form of hypertension during pregnancy. We will close with a viewpoint on future research directions and implications for developing novel therapies.