The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease.

The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease.
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DOI:
10.1055/a-1128-0421
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发表时间:
2020-06
期刊:
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
影响因子:
--
通讯作者:
Rainey WE
Rainey WE
中科院分区:
其他
文献类型:
--
作者:
Lim JS;Rainey WE

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原发性醛固酮增多症(PA)是继发性高血压最常见的原因。PA的标志是在肾素抑制的情况下肾上腺产生醛固酮。PA亚型包括肾上腺单侧和双侧醛固酮增多症。在确定体细胞基因突变在醛固酮腺瘤(阿帕)中的作用方面取得了相当大的进展,APA是单侧PA的主要原因。这包括使用下一代测序(NGS)来确定阿帕中的复发性体细胞突变,这些突变破坏钙信号传导,增加醛固酮合酶(CYP11B2)表达和醛固酮产生。对正常人、单侧和双侧PA患者肾上腺进行CYP11B2免疫组织化学染色,可以识别CYP11B2阳性细胞灶,称为醛固酮生成细胞簇(APCC)。APCC位于肾上腺被膜下,与阿帕一样,许多APCC具有已知增加醛固酮产生的体细胞基因突变。这些结果表明,APCC可能在PA的病理进展中发挥作用。在此,我们提供了最近的研究,旨在表征APCC的更新,并讨论了未回答的问题有关的APCC在PA中的作用。
Primary aldosteronism (PA) is the most common cause of secondary hypertension. The hallmark of PA is adrenal production of aldosterone under suppressed renin conditions. PA subtypes include adrenal unilateral and bilateral hyperaldosteronism. Considerable progress has been made in defining the role for somatic gene mutations in aldosterone-producing adenomas (APA) as the primary cause of unilateral PA. This includes the use of next-generation sequencing (NGS) to define recurrent somatic mutations in APA that disrupt calcium signaling, increase aldosterone synthase (CYP11B2) expression, and aldosterone production. The use of CYP11B2 immunohistochemistry on adrenal glands from normal subjects, patients with unilateral and bilateral PA has allowed the identification of CYP11B2-positive cell foci, termed aldosterone-producing cell clusters (APCC). APCC lie beneath the adrenal capsule and like APA, many APCC harbor somatic gene mutations known to increase aldosterone production. These findings suggest that APCC may play a role in pathologic progression of PA. Herein, we provide an update on recent research directed at characterizing APCC and also discuss the unanswered questions related to the role of APCC in PA.
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