The Journal of clinical endocrinology and metabolism · 2013
Human red blood cells alterations in primary aldosteronism.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Bordin Luciana, Donà Gabriella, Sabbadin Chiara, Ragazzi Eugenio, Andrisani Alessandra, Ambrosini Guido, Brunati Anna Maria, Clari Giulio, Armanini Decio
Аннотация
CONTEXT: Aldosterone (Aldo) effects include NADPH oxidase activation involved in Aldo-related oxidative stress. Red blood cells (RBCs) are particularly sensitive to oxidative assault, and both the formation of high molecular weight aggregates (HMWAs) and the diamide-induced Tyr phosphorylation (Tyr-P) level of membrane band 3 can be used to monitor their redox status.
OBJECTIVE: The Aldo-related alterations in erythrocytes were evaluated by comparing in vitro evidence.
DESIGN: This was a multicenter comparative study.
STUDY PARTICIPANTS: The study included 12 patients affected by primary aldosteronism (PA) and 6 healthy control subjects (HCs), whose RBCs were compared with those of patients with PA. For in vitro experiments, RBCs from HCs were incubated with increasing Aldo concentrations.
MAIN OUTCOME MEASURES: The Tyr-P level, band 3 HMWA formation, and autologous IgG binding were evaluated.
RESULTS: In patients with PA, both Tyr-P levels and band 3 HMWAs were higher than those in HCs. RBCs from HCs were treated with increasing Aldo concentrations in both platelet-poor plasma (PPP) and charcoal-stripped (CS)-PPP. Results showed that Aldo had dose- and time-dependent effects on band 3 Tyr-P and HMWA formation in CS-PPP more than in PPP. These effects were almost completely prevented by canrenone or cortisol. Aldo-related membrane alterations led to increased autologous IgG binding.
CONCLUSIONS: Erythrocytes from patients with PA show oxidative-like stress evidenced by increased HMWA content and diamide-induced band 3 Tyr-P level. Aldo effects are mediated by the mineralocorticoid receptor, as suggested by the inhibitory effects of canrenone, an antagonist of Aldo. In CS-PPP, in which Aldo induces remarkable membrane alterations leading to IgG binding, Aldo may be responsible for premature RBC removal from circulation.
OBJECTIVE: The Aldo-related alterations in erythrocytes were evaluated by comparing in vitro evidence.
DESIGN: This was a multicenter comparative study.
STUDY PARTICIPANTS: The study included 12 patients affected by primary aldosteronism (PA) and 6 healthy control subjects (HCs), whose RBCs were compared with those of patients with PA. For in vitro experiments, RBCs from HCs were incubated with increasing Aldo concentrations.
MAIN OUTCOME MEASURES: The Tyr-P level, band 3 HMWA formation, and autologous IgG binding were evaluated.
RESULTS: In patients with PA, both Tyr-P levels and band 3 HMWAs were higher than those in HCs. RBCs from HCs were treated with increasing Aldo concentrations in both platelet-poor plasma (PPP) and charcoal-stripped (CS)-PPP. Results showed that Aldo had dose- and time-dependent effects on band 3 Tyr-P and HMWA formation in CS-PPP more than in PPP. These effects were almost completely prevented by canrenone or cortisol. Aldo-related membrane alterations led to increased autologous IgG binding.
CONCLUSIONS: Erythrocytes from patients with PA show oxidative-like stress evidenced by increased HMWA content and diamide-induced band 3 Tyr-P level. Aldo effects are mediated by the mineralocorticoid receptor, as suggested by the inhibitory effects of canrenone, an antagonist of Aldo. In CS-PPP, in which Aldo induces remarkable membrane alterations leading to IgG binding, Aldo may be responsible for premature RBC removal from circulation.