Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity

Hayashi, Taiki; Zhang, Zhen; Al-Eyd, Ghaith; Sasaki, Atsushi; Yasuda, Masanori; Oyama, Masafumi; Gómez-Sánchez, Celso E.; Asakura, Hirotaka; Seki, Tsugio; Mukai, Kuniaki; Nishimoto, Katsutaro

doi:10.1016/j.jsbmb.2019.04.010

Cited by 17 publications

(17 citation statements)

References 30 publications

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“…Another group defined "aldosterone-producing micronodules" as "CYP11B2-positive cortical micronodules located in the CYP11B2-negative ZG" [11,17]. These lesions appear to be similar to pAATLs and small APA lesions [7,10]. Thus, we and others have utilized multiple terms to describe different types of PA lesions, and none of them may be sufficiently complete or comprehensive.…”

Section: Discussionmentioning

confidence: 99%

Diverse pathological lesions of primary aldosteronism and their clinical significance

Nishimoto

Umakoshi

Seki³

et al. 2021

Hypertens Res

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Primary aldosteronism (PA) is mainly clinically classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (n = 85), partial success (n = 19), and absent success (n = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2–6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.

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Section: Discussionmentioning

confidence: 99%

Diverse pathological lesions of primary aldosteronism and their clinical significance

Nishimoto

Umakoshi

Seki³

et al. 2021

Hypertens Res

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“…Two clones (13 and 17) differing only by their titer, were obtained that detect the identical single band on western blot and immunostaining. Another research group also described a similar CYP11B2 monoclonal antibody produced against a peptide of the same sequence [34,35].…”

Section: Immunohistochemistry Of Normal Human Adrenalsmentioning

confidence: 99%

“…1d) [36,38]. In older individuals, CYP11B2 immunoreactivity occurs in clusters of cells adjacent to the adrenal capsule surrounded by cells with no CYP11B2 staining named aldosterone-producing cell clusters (APCC) [33,35,38]. APCC exhibit strong uniform immunoreactivity for CYP11B2 and are 0.2-1.5 mm in width and 0.1-0.5 mm in depth measured as distance perpendicular to the capsule.…”

Section: Normal Adrenal Cortexmentioning

confidence: 99%

“…The age of appearance of APCC correlates with the increased incidence of hypertension in which aldosterone may have a role [38,42]. The decrease in the number of APCC described in adrenals of individuals older than 70 years might represent a survival advantage for those with fewer APCC, rather than a decrease of APCC with age [35].…”

Section: Normal Adrenal Cortexmentioning

confidence: 99%

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Immunohistochemistry of the Human Adrenal CYP11B2 in Normal Individuals and in Patients with Primary Aldosteronism

Gómez-Sánchez

Nishimoto

2020

Horm Metab Res

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The CYP11B2 enzyme is the terminal enzyme in the biosynthesis of aldosterone. Immunohistochemistry using antibodies against CYP11B2 defines cells of the adrenal ZG that synthesize aldosterone. CYP11B2 expression is normally stimulated by angiotensin II, but becomes autonomous in primary hyperaldosteronism, in most cases driven by recently discovered somatic mutations of ion channels or pumps. Cells expressing CYP11B2 in young normal humans form a continuous band beneath the adrenal capsule; in older individuals they form discrete clusters, aldosterone-producing cell clusters (APCC), surrounded by non-aldosterone producing cells in the outer layer of the adrenal gland. Aldosterone-producing adenomas may exhibit a uniform or heterogeneous expression of CYP11B2. APCC frequently persist in the adrenal with an aldosterone-producing adenoma suggesting autonomous CYP11B2 expression in these cells as well. This was confirmed by finding known mutations that drive aldosterone production in adenomas in the APCC of clinically normal people. Unilateral aldosteronism may also be due to multiple CYP11B2-expressing nodules of various sizes or a continuous band of hyperplastic ZG cells expressing CYP11B2. Use of CYP11B2 antibodies to identify areas for sequencing has greatly facilitated the detection of aldosterone-driving mutations.

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“…This might support the hypothesis that APCCs are the initial lesions and APAs originate from these areas (the second-hit mutation may be the reason for this transition). The study by Hayashi et al associates the presence of APCCs and AATLs with longevity, with the conclusion that the decrease in aldosterone production might have survival advantages (26). Despite the great progress, further studies are needed for better understanding of the discoveries that for now have shaken up of our notion of primary aldosteronism classification and pathogenesis (22).…”

Section: Bilateral Primary Aldosteronism Still Idiopathic or Not?mentioning

confidence: 99%

Primary aldosteronism – the expanding spectrum of unsolved practical issues

Łebek-Szatańska

Papierska²

2020

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Primary aldosteronism is the most frequent cause of hormonal hypertension. Recent findings support the concept of continuous spectrum of autonomous aldosterone secretion with mild or subclinical forms being even more common than was suspected. Assumptions emerge that a considerable number of low-renin hypertensives might actually have aldosterone overproduction. However, the awareness of the disease and its consequences is still unsatisfactory. Nowadays experts are still trying to manage some unanswered questions and on-going debate on who should be screened for primary aldosteronism and how to do so.

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Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity

Cited by 17 publications

References 30 publications

Diverse pathological lesions of primary aldosteronism and their clinical significance

Diverse pathological lesions of primary aldosteronism and their clinical significance

Immunohistochemistry of the Human Adrenal CYP11B2 in Normal Individuals and in Patients with Primary Aldosteronism

Primary aldosteronism – the expanding spectrum of unsolved practical issues

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