Hypothesis on a relationship between hyperaldosteronism, inflammation, somatic mutations, and autoimmunity

Abstract

After the description of the adaption syndrome, Selye hypothesized in 1949 that desoxycorticosterone (DOC), the first mineralocorticoid to be discovered, could induce an inflammatory effect. This hypothesis was based on the effect of DOC in worsening the symptoms of rheumatoid arthritis and inducing a strong inflammatory effect in animal models. THE ROLE OF ANTI-TYPE 1 ANGIOTENSIN RECEPTORS ANTIBODIE AND INFLAMMATION IN PARecent studies have shown an association between elevated levels of autoantibodies against the angiotensin type 1 receptor (AT1R-AAs) and primary and secondary aldosteronism. Subsequent studies have shown that AT1R-AAs are able to activate NADPH-oxidase, tumor necrosis factor-α, and nuclear factor-kB, contributing to the increased production of reactive oxygen species related to the genomic and nongenomic inflammatory effects of aldosterone. 15 Moreover, these proinflammatory factors could induce not only autoimmune disorders but also somatic mutations in nearby cells.16.Recent advances in genome technology have allowed the discovery of recurrent somatic mutations in genes coding for ion channels and adenosine triphosphatases regulating intracellular ionic homeostasis and membrane potential, which could lead to increased aldosterone production and adrenal cortex cell proliferation. 17 Currently, about 50% of sporadic aldosterone-producing adenoma (APA) cases have been associated with some genetic defect. THE ONSET OF PA AND THE THEORY OF EVOLUTIONThe pathogenesis of PA remains unknown. It is difficult to understand CONCLUSIONSAll of these hypotheses should be investigated, and the notion that PA is a syndrome with different mechanisms involved in the individual case should not be excluded. DISCLOSURESThe authors have no conflicts of interest to disclose.

Uterine fibroids and risk of hypertension: Implication of inflammation and a possible role of the renin‐angiotensin‐aldosterone system

“…We have hypothesized a relationship between inflammation, aldosterone, and somatic mutations . Recurrent somatic mutations have been involved in increased aldosterone production and adrenal cortex cell proliferation .…”

“…12 The increased cardiovascular risk due to aldosterone is evident in We have hypothesized a relationship between inflammation, aldosterone, and somatic mutations. 16 Recurrent somatic mutations have been involved in increased aldosterone production and adrenal cortex cell proliferation. 17 Currently, about 50% of sporadic aldosterone-producing adenoma cases have been associated with some genetic defects.…”

Relationship between water and salt intake, osmolality, vasopressin, and aldosterone in the regulation of blood pressure

“…It is well known that aldosterone has another important effect beyond the regulation of water‐electrolyte balance: it shows a proinflammatory action, responsible for the profibrotic effects associated with cardiovascular risk . It is worthy of note that inflammation and cardiovascular complications are also present in secondary aldosteronism, independently from the increase in BP or sodium.…”

“…It is well known that aldosterone has another important effect beyond the regulation of water-electrolyte balance: it shows a proinflammatory action, responsible for the profibrotic effects associated with cardiovascular risk. 10 It is worthy of note that inflammation and cardiovascular complications are also present in secondary aldosteronism, independently from the increase in BP or sodium. From these observations, it seems that sodium and hypertension are not strictly necessary for induction of aldosterone-related profibrotic effects, while they are primarily involved in the increase in BP.…”

Relationship between sodium, pentraxin‐3 and aldosterone in inflammation and cardiovascular risk

“…In the recent years, the involvement of inflammation in hypertension and its complications has been extensively evaluated. Inflammation can be linked to high‐sodium intake or an excess of aldosterone, increasing local and systemic inflammatory reaction mediated by T cells and macrophages …”