Oxidative stress-related proteins in a Conn's adenoma tissue. Relevance for aldosterone's prooxidative and proinflammatory activity.
OBJECTIVE
Angiotensin II (Ang II) induces oxidative stress (OxSt), which is essential for cardiovascular remodeling. Aldosterone also induces fibrosis and remodeling through direct effect on non-classical mineralocorticoid (MR) target tissues. However, studies on the role of aldosterone on OxSt and related factors in humans are lacking.


METHODS
We assessed gene and protein expression of p22phox (RT-PCR and Western blot), NAD(P)H oxidase subunit essential for superoxide production and gene expression of transforming growth fator (TGF) beta, plasminogen activator inhibitor (PAI)-1, and heme oxygenase (HO)-1, effectors of OxSt (RT-PCR), in a Conn's adenoma, removed from a patient with primary hyperaldosteronism. Ang II type 1 (AT1R) and MR receptors expression were also evaluated (RT-PCR). The normal adrenal tissue adjacent to the adenoma was used as control.


RESULTS
p22phox gene and protein expression were higher (31% and 53%, respectively) in the adrenal adenoma. TGFbeta, PAI-1, and HO-1 gene expression were also higher (25%, 129%, and 25%, respectively) in the adrenal adenoma while AT1R gene expression was similar (8%). The expression of MR in the adenoma was documented.


CONCLUSIONS
This report demonstrates in a human model that the increased aldosterone production has effects on enzyme systems related to OxSt, enhancing the systemic fibrogenic effects of aldosterone excess through TGFbeta and PAI-1 expression which was previously demonstrated only indirectly in vitro and in animal models. The presence of MR expression in the adenoma may link the hormone with the adenoma growth. Therefore, the results of this study derived from a single case might represent an important working hypothesis for further research in a larger number of cases to clarify the role of aldosterone overproduction on OxSt and its clinical relevance.
Calò
L A
LA
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padua, Via Giustiniani 2,Padua, Italy. renzcalo@unipd.it
Pagnin
E
E
Davis
P A
PA
Armanini
D
D
Mormino
P
P
Rossi
G P
GP
Pessina
A C
AC
D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000503:physiopathology*; D000311:Adrenal Glands / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000503:physiopathology*; D000328:Adult; D000450:Aldosterone / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006929:Hyperaldosteronism / Q000601:surgery; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D016212:Transforming Growth Factor beta; D000450:Aldosterone; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human