Eplerenone mimics features of the alternative activation in macrophages obtained from patients with heart failure and healthy volunteers
| Autor: | Grzegorz Machnik, Krzysztof Łabuzek, Sebastian Liber, Łukasz Bułdak, Joanna Krupej-Kędzierska, Magdalena Bobrzyk, Bogusław Okopień |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival medicine.drug_class Nitric Oxide Synthase Type II Receptors Cell Surface Spironolactone Biology Nitric Oxide chemistry.chemical_compound Mineralocorticoid receptor Internal medicine medicine Humans Drug Interactions Lectins C-Type Receptor Aldosterone Aged Mineralocorticoid Receptor Antagonists Heart Failure Pharmacology Arginase Superoxide Dismutase Macrophages Macrophage Activation Middle Aged medicine.disease Healthy Volunteers Eplerenone Mannose-Binding Lectins Phenotype Receptors Mineralocorticoid Endocrinology Gene Expression Regulation chemistry Mineralocorticoid Heart failure Female Interleukin-4 Reactive Oxygen Species Mannose Receptor Mannose receptor medicine.drug |
| Zdroj: | European Journal of Pharmacology. 726:96-108 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2014.01.043 |
| Popis: | Alternative activation of macrophages plays protective role in cardiac remodelling in heart failure and the activity of mineralocorticoid receptor may determine the phenotype of these cells. We examined the influence of eplerenone, aldosterone, and IL-4 on descriptors of alternative activation in blood monocytes collected from 19 patients with heart-failure and 20 healthy volunteers. “Heart failure” macrophages in comparison with “healthy” macrophages had increased mineralocorticoid activity, NO and reactive oxygen species production, expression of iNOS mRNA and protein, but decreased expression of arginase I and mannose receptor proteins, and activity of MnSOD and CuZnSOD. Aldosterone increased mineralocorticoid activity, NO and reactive oxygen species production, iNOS mRNA and protein expression, MnSOD and CuZnSOD activity. Eplerenone attenuated the effects of aldosterone on all but MnSOD and CuZnSOD variables. Eplerenone alone increased the production of NO, MnSOD and CuZnSOD activity, arginase I gene and protein expression, and mannose receptor gene and protein expression, but decreased mineralocorticoid activity only in “heart failure” macrophages. The latter suggests altered function of mineralocorticoid receptor in heart failure. Increased mineralocorticoid activity accounts for increased NO production, iNOS gene and protein expression but does not explain the increased basal reactive oxygen species production and decreased markers of alternative activation in “heart failure” macrophages. In the lack of change in basal mineralocorticoid activity, eplerenone increases markers of alternative activation in a mineralocorticoid receptor-independent manner. Because of changes in iNOS and NO variable, eplerenone induced qualitatively different activation of macrophages from that obtained with IL-4. |
| Databáze: | OpenAIRE |
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