Prerequisite for Cardiac Aldosterone Action
| Autor: | Nicolette Farman, Nadia Alfaidy, Jean-Pierre Bonvalet, Emmanuel Eugène, Marc Lombès, Alessandro Lessana |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class medicine.medical_treatment Gene Expression In situ hybridization 030204 cardiovascular system & hematology Immunoenzyme Techniques 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Mineralocorticoid receptor Ventricular hypertrophy Physiology (medical) Internal medicine medicine Humans RNA Messenger Receptor Aldosterone In Situ Hybridization 030304 developmental biology Heart transplantation 0303 health sciences business.industry Myocardium Hydroxysteroid Dehydrogenases Heart RNA Probes medicine.disease Transplantation Receptors Mineralocorticoid Endocrinology chemistry Mineralocorticoid 11-beta-Hydroxysteroid Dehydrogenases Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 92:175-182 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.92.2.175 |
| Popis: | Background It has been proposed that aldosterone exerts direct effects on heart function, most notably on the development of myocardial fibrosis during ventricular hypertrophy in rat. Initial events in aldosterone action entail its binding to mineralocorticoid receptor (MR). Because MR displays similar affinities for aldosterone and glucocorticoids, the in vivo aldosterone selectivity of MR requires the presence of an enzyme, 11β-hydroxysteroid dehydrogenase (11-HSD), which metabolizes glucocorticoids into inactive derivatives. Although evidence exists for the presence of MR in rodent heart, no data are available for humans; moreover, the existence of cardiac 11-HSD is controversial. Methods and Results The heart samples used originated from tissue removed during cardiac surgery in nontransplant patients or from endocavitary biopsies done for the follow-up of heart transplantation. The expression of MR was examined at the mRNA and protein level by in situ hybridization with cRNA probes specific for human MR mRNA and by immunodetection with two specific anti-MR antibodies. 11-HSD catalytic activity was determined by measurement of the metabolic rate of tritiated corticosteroids by cardiac samples. In nontransplanted hearts, an in situ hybridization signal equivalent to that found in the whole kidney was present on cardiomyocytes. Specific immunolabeling of cardiomyocytes with anti-MR antibodies demonstrated the presence of the MR protein. Cardiac 11-HSD activity was detected (243±26 fmol · 30 min −1 · mg protein −1 ) and was dependent on the cofactor NAD, not NADP, suggesting that it corresponds to the form of the enzyme specifically responsible for MR protection. In transplanted hearts that presented severe alterations, MR immunodetection was weaker and irregular, with no specific hybridization signal. Conclusions Our results demonstrate that MR is coexpressed with 11-HSD in human heart, which thus possesses the cellular machinery required for direct aldosterone action. |
| Databáze: | OpenAIRE |
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