Primary aldosteronism: a channelopathy?
Primary aldosteronism: a channelopathy?
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原发性醛固酮增多症：通道病？
DOI：
10.1161/hypertensionaha.113.02335
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Gomez-Sanchez,CelsoE
中科院分区：
文献类型：
--
作者：
Gomez-Sanchez,CelsoE
synthesis to a similar degree that the delI157 KCNJ5, which was used as a positive control. 7 Transfection of all 3 variants, R52H, E246K, and E282Q, enhanced the angiotensin II stimulation of aldosterone secretion. In previous studies, the KCNJ5 mutant T158A resulted in a significant increase in basal, as well as AII-, forskolin-, and potassium-stimulated aldosterone, cortisol, and 18-oxocortisol production by the HAC15 cells. 6Aldosterone secretion in most patients with APA is sensitive to stimulation with ACTH and less so with angiotensin II, whereas in IHA, aldosterone secretion is sensitive to angiotensin II stimulation. This finding has been used in the design of the postural maneuver to distinguish between the 2 conditions. Some APAs (10% to 30%) also are angiotensin II responsive, which behave as IHA in this maneuver. An important finding not mentioned in the discussion of the article by Murthy et al7 is that the 3 new genomic mutations, R52H, E246K, and G247R, occurred in patients with IHA. In their cohort of 251 patients with PA, 12 had the E282Q polymorphism and of these 9 had IHA. There were no clinical details on these patients or on the histopathology of the adenomas of the 3 APA patients with the E282Q polymorphism. 7 Many adrenals with an APA, including those with KCNJ5 mutations, also have zona glomerulosa hyperplasia with nodules and aldosterone-producing cell clusters surrounding the adenoma, which also express stem/proliferative gene markers. 8 The functional relevance of these areas is unknown. The pathophysiological characteristics of the zona glomerulosa surrounding the APA might depend on the functional consequences of the type of KCNJ5 mutation in the adenoma. Because patients with IHA tend to respond to postural maneuvers that stimulate angiotensin II, one may hypothesize that APA patients with the E282Q might have an angiotensin II–responsive adenoma.
