Regulation of aldosterone secretion by Cav1.3

Xie, Catherine; Shaikh, Lalarukh Haris; Garg, Shivam; Tanriver, Gizem; Teo, Ada; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B.; Azizan, Elena

doi:10.1038/srep24697

Cited by 34 publications

(27 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MUT could be tested ex vivo (46), with limited informative value beyond our studies in H295R cells. The most promising path forward, however, involves clinical trials in humans.…”

Section: Discussionmentioning

confidence: 99%

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

Scholl

Abriola

Zhang

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

tributed to cell maintenance. LA, UIS, and JSM designed and performed high-throughput screening assays. MP synthesized compounds. CZ and WW performed and analyzed electrophysiology. ENR performed qPCR analysis and ELISAs. UIS and BIK performed Kirby-Bauer disk-diffusion assays. UIS prepared figures and tables. UIS and RPL wrote and edited the main text and supplemental data. UIS, DH, JSM, WW, and RPL oversaw parts of the project or had advisory roles.

show abstract

“…MUT could be tested ex vivo (46), with limited informative value beyond our studies in H295R cells. The most promising path forward, however, involves clinical trials in humans.…”

Section: Discussionmentioning

confidence: 99%

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

Scholl

Abriola

Zhang

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…Gene targeted NGS analysis of DNA from 99 APCC from the 15 BHA adrenals demonstrated that CACNA1D mutations (58 %) were present at a higher prevalence than past seen in normal adrenals [15]. Interestingly, in vitro adrenal cell-based studies have shown that expression of mutated CAC-NA1D increases aldosterone production and this production could be significantly reduced by the calcium channel blocker, nifedipine [75]. The high prevalence of APCC with CACNA1D mutations suggests that research on the efficacy of calcium channel blockers as an inhibitor of BHA aldosterone overproduction should be further examined.…”

Section: Apcc In Preclinical and Overt Primary Aldosteronismmentioning

confidence: 99%

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

Lim

Rainey

2020

Horm Metab Res

View full text Add to dashboard Cite

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.

show abstract

“…Importantly, a recent study showed that excess aldosterone caused by CACNA1D mutations could be inhibited by calcium channel blockers [27], suggesting that such drugs might be useful for APCC-oriented aldosterone overproduction. The current findings support a contribution of APCC to unilateral CT-negative PA, but an APCC role in the more common bilateral CT-negative PA (IHA) remains to be determined.…”

Section: Apcc To Ct-negative Pa Pathwaymentioning

confidence: 99%

Aldosterone-Producing Cell Clusters in Normal and Pathological States

2017

View full text Add to dashboard Cite

Primary aldosteronism (PA) plays an important role for the risk of cardiovascular complications, and early diagnosis and targeted treatment in the early states based on its pathophysiology is warranted. Next-generation sequencing (NGS) has revealed recurrent somatic mutations in aldosterone-driving genes in aldosterone-producing adenoma (APA). By applying CYP11B2 (aldosterone synthase) immunohistochemistry and NGS to adrenal glands from normal subjects and PA patients, we and others have shown that CYP11B2-positive cells make small clusters, termed aldosterone-producing cell clusters (APCC), beneath adrenal capsule and harbor somatic mutations in genes mutated in APA. We have shown that APCC are increased in CT-negative PA adrenals, while others showed potential progression from APCC to micro APA through mutations. These results suggest that APCC are a key factor for understanding the origin of PA, and further investigation on the relation between APCC and PA is highly needed.

show abstract

Regulation of aldosterone secretion by Cav1.3

Cited by 34 publications

References 42 publications

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

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

Aldosterone-Producing Cell Clusters in Normal and Pathological States

Contact Info

Product

Resources

About