Oxidative stress related proteins in a Conn’s adenoma tissue

Abstract

Activation of renin-angiotensin-aldosterone system is deemed to play a major role in the induction of oxidative stress (OxSt)via up regulation of NAD(P)H oxidase with ensuing angiotensin II (AngII)-triggered OxSt. AngII effects on remodeling and atherogenesis can occur mostly through activation of redox sensitive genes. Aldosterone is also important factor in causing endothelial dysfunction, fibrosis and remodeling through direct effect on non classical target tissues such as the vascular wall, heart and kidney. However human studies on the role of Aldosterone on OxSt and OxSt related factors are lacking.Hence, in a Conn's adenoma (CA) where aldosterone is highly produced, which was surgically removed from a patient with primary hyperaldosteronism we studied the expression of genes and protein (RT-PCR and Western blot analysis, expressed as densitometric units (d.u.) using β actin for normalization) of p22phox, the NAD(P)H subunit essential for O2- production. We also assessed with the same tools the gene expression of TGFβ a major profibrotic cytokine, effector of OxSt, of PAI-1, profibrotic and prothrombotic factor, of HO-1, induced by OxSt and of AngII receptors type 1 (AT1).The normal adrenal tissue adiacent to the adenoma was used as control. p22phox gene and protein expression were higher in the adrenal adenoma (31% and 56% respectively), (0.5 vs 0.38 d.u. and 0.69 vs 0.44 respectively). TGFβ, PAI-1 and HO-1 gene expression were also higher in the adrenal adenoma (25%, 129% and 25% respectively) (0.78 d.u. vs 0.62; 0.39 vs 0.17; 0.49 vs 0.39 respectively) while AT1 gene expression was similar (8%) (0.54 d.u. vs 0.5). Elevation of these OxSt related proteins where aldosterone is highly produced, such as adrenal adenoma, supports a linkage of Aldosterone with OxSt. The increased p22phox gene expression in CA compared to normal adiacent adreocortical tissue provides a mechanism for the increased production of ROS which can enhance the systemic fibrogenetic effects of excess aldosterone by acting through TGFβ and PAI-1 gene expression. This report represents the first clinically based evidence in a human condition associated with increased aldosterone production of aldosterone's effect on enzyme systems related to OxSt which has previously been demonstrated only indirectly in “in vitro” and animal studies.