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Mass Spectrometry Imaging Establishes 2 Distinct Metabolic Phenotypes of Aldosterone-Producing Cell Clusters in Primary Aldosteronism
Hypertension ( IF 8.3 ) Pub Date : 2020-03-01 , DOI: 10.1161/hypertensionaha.119.14041
Na Sun 1 , Lucie S Meyer 2 , Annette Feuchtinger 1 , Thomas Kunzke 1 , Thomas Knösel 3 , Martin Reincke 2 , Axel Walch 1 , Tracy Ann Williams 2, 4
Affiliation  

Supplemental Digital Content is available in the text. Aldosterone-producing adenomas (APAs) are one of the main causes of primary aldosteronism and the most prevalent surgically correctable form of hypertension. Aldosterone-producing cell clusters (APCCs) comprise tight nests of zona glomerulosa cells, strongly positive for CYP11B2 (aldosterone synthase) in immunohistochemistry. APCCs have been suggested as possible precursors of APAs because they frequently carry driver mutations for constitutive aldosterone production, and a few adrenal lesions with histopathologic features of both APCCs and APAs have been identified. Our objective was to investigate the metabolic phenotypes of APCCs (n=27) compared with APAs (n=6) using in situ matrix-assisted laser desorption/ionization mass spectrometry imaging of formalin-fixed paraffin-embedded adrenals from patients with unilateral primary aldosteronism. Specific distribution patterns of metabolites were associated with APCCs and classified 2 separate APCC subgroups (subgroups 1 and 2) indistinguishable by CYP11B2 immunohistochemistry. Metabolic profiles of APCCs in subgroup 1 were tightly clustered and distinct from subgroup 2 and APAs. Multiple APCCs from the same adrenal displayed metabolic profiles of the same subgroup. Metabolites of APCC subgroup 2 were highly similar to the APA group and indicated enhanced metabolic pathways favoring cell proliferation compared with APCC subgroup 1. In conclusion, we demonstrate specific subgroups of APCCs with strikingly divergent distribution patterns of metabolites. One subgroup displays a metabolic phenotype convergent with APAs and may represent the progression of APCCs to APAs.

中文翻译:

质谱成像确定原发性醛固酮增多症中醛固酮生成细胞簇的 2 种不同代谢表型

补充数字内容在文本中可用。醛固酮腺瘤 (APAs) 是原发性醛固酮增多症的主要原因之一,也是最常见的可通过手术矫正的高血压形式。醛固酮生成细胞簇 (APCC) 包含肾小球带细胞的紧密巢穴,免疫组织化学中 CYP11B2(醛固酮合酶)呈强阳性。APCCs 被认为可能是 APAs 的前体,因为它们经常携带组成性醛固酮产生的驱动突变,并且已经确定了一些具有 APCCs 和 APAs 组织病理学特征的肾上腺病变。我们的目标是使用原位基质辅助激光解吸/电离质谱成像对单侧原发性醛固酮增多症患者的福尔马林固定石蜡包埋肾上腺进行比较 APCC(n=27)与 APA(n=6)的代谢表型. 代谢物的特定分布模式与 APCC 相关,并且将 CYP11B2 免疫组织化学无法区分的 2 个单独的 APCC 亚组(亚组 1 和 2)分类。亚组 1 中 APCC 的代谢谱紧密聚集并且与亚组 2 和 APA 不同。来自同一肾上腺的多个 APCC 显示出同一亚组的代谢特征。APCC 亚组 2 的代谢物与 APA 组高度相似,表明与 APCC 亚组 1 相比有利于细胞增殖的代谢途径增强。 总之,我们展示了具有惊人不同代谢物分布模式的特定 APCC 亚群。一个亚组显示与 APAs 趋同的代谢表型,可能代表 APCCs 向 APAs 的进展。
更新日期:2020-03-01
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