Oxidative stress and profibrotic action of aldosterone

We have read with great interest the recent paper of Iglarz et al1 published in the July issue of the Journal detailing their studies on the profibrotic action of aldosterone. They concluded that the profibrotic activity of aldosterone involves oxidative stress, at least in part, via an interaction with the renin-angiotensin system. We would like to provide further support to the contention of a specific profibrotic action of aldosterone with the demonstration ex vivo in human mononuclear cells, recently published from our laboratory,2 that indicates that aldosterone has a direct effect on oxidative stress through its ability to increase the levels of p22phox, an important subunit of NADPH oxidase, as well as of a recognized profibrotic protein, PAI-1, which may provide a direct link to the profibrotic action of aldosterone. Our findings were further strengthened by the observations demonstrating similar effects of glycyrrhetinic acid,2 a constituent of licorice root, which is known to have a direct mineralocorticoid-like effect when consumed in high amounts.3 Thus, the report of Iglarz et al1 in combination with our study provides clear evidence for the centrality of ROS mediated events in the pathophysiology of aldosterone-related profibrotic effects. These findings are important given the growing recognition of the role of aldosterone in the pathophysiology of cardiovascular disease, as demonstrated by the results of the recently concluded the Randomized Aldactone Evaluation Study (RALES)4 and the EPlerenone neuroHormonal Efficacy and SUrvival Study (EPHESUS)5 documenting a decline in overall mortality associated with the use of mineralcorticoid receptor antagonists in patients with advanced heart failure. The findings from these trials, in fact, indicated that the treatment to directly reduce aldosterone's effects through receptor blocking in addition to treating with drugs that reduce the activity of the renin-angiotensin system, will provide additional benefits to patients with cardiovascular disease.