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• W2038450757 abstract "To the Editor: The recognition of the inflammatory and profibrotic role of aldosterone in the pathophysiology of cardiovascular disease, via its effect on endothelial dysfunction, is of growing importance, as demonstrated by the results of the recently concluded Randomized Aldactone Evaluation Study (RALES)1.Pitt B. Zannad F. Remme W.J. et al.The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.N Engl J Med. 1999; 341: 709-717Crossref PubMed Scopus (7097) Google Scholar, and the EPlerenone neuroHormonal Efficacy and SUrvival Study (EPHESUS)2.Pitt B. Remme W. Zannad F. et al.Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med. 2003; 348: 1309-1321Crossref PubMed Scopus (3842) Google Scholar. These studies have, in fact, indicated the reduction of aldosterone effects through receptor blocking as additional benefit to patients with cardiovascular diseases. In a paper published in the May issue Kidney International, Oberleithner documented “in vitro” an aldosterone remodeling effect on human endothelium through induction of cell stiffness due to a presumably aldosterone induced oxidative stress via modulation of NAD(P)H oxidase3.Oberleithner H. Aldosterone makes human endothelium stiff and vulnerable.Kidney Int. 2005; 67: 1680-1682Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar. We would like to provide further support to the contention of a specific remodeling and profibrotic action of aldosterone with the demonstration “ex vivo” in human mononuclear cells, recently published by our laboratory4.Cali L.A. Zaghetto F. Pagnin E. et al.Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes.J Clin Endocrinol Metab. 2004; 89: 1973-1976Crossref Scopus (89) Google Scholar, 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, essential for superoxide anion generation. It, in fact, functions as an integral subunit of the final electron transport from NADPH to heme and molecular oxygen in generating superoxide anions. The aldosterone-induced increased level of PAI-1, a recognized profibrotic protein, we have shown in the same study4.Cali L.A. Zaghetto F. Pagnin E. et al.Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes.J Clin Endocrinol Metab. 2004; 89: 1973-1976Crossref Scopus (89) Google Scholar, may also provide a direct link to the cardiovascular profibrotic and remodeling action of aldosterone. Our findings were further strengthened by similar effects shown by glycyrrhetinic acid4.Cali L.A. Zaghetto F. Pagnin E. et al.Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes.J Clin Endocrinol Metab. 2004; 89: 1973-1976Crossref Scopus (89) Google Scholar, a constituent of licorice root, which is known to have a direct mineralocorticoid-like effect5.Armanini D. Lewicka S. Pratesi C. et al.Further studies on the mechanism of the mineralocorticoid action of licorice in humans.J Endocrinol Invest. 1996; 19: 624-629Crossref PubMed Scopus (43) Google Scholar. Thus, the report of Oberleithner3.Oberleithner H. Aldosterone makes human endothelium stiff and vulnerable.Kidney Int. 2005; 67: 1680-1682Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar in combination with the results of our study provides clear evidence for the aldosterone-related vascular remodeling effects through its induction of oxidative stress and oxidative stress-related profibrotic molecules, such as PAI-14.Cali L.A. Zaghetto F. Pagnin E. et al.Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes.J Clin Endocrinol Metab. 2004; 89: 1973-1976Crossref Scopus (89) Google Scholar." @default.
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• W2038450757 date "2005-10-01" @default.
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• W2038450757 title "Aldosterone-mediated endothelial remodeling and oxidative stress" @default.
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• W2038450757 doi "https://doi.org/10.1038/ki.2005.4496300" @default.
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