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Upregulation of myocardial estrogen receptors in human aortic stenosis.
- Source :
-
Circulation [Circulation] 2004 Nov 16; Vol. 110 (20), pp. 3270-5. Date of Electronic Publication: 2004 Nov 08. - Publication Year :
- 2004
-
Abstract
- Background: Estrogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes.<br />Methods and Results: ER-alpha and -beta, calcineurin A-beta, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-alpha mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA.<br />Conclusions: ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.
- Subjects :
- Adrenergic beta-Antagonists pharmacology
Adrenergic beta-Antagonists therapeutic use
Angiotensin II Type 1 Receptor Blockers pharmacology
Angiotensin II Type 1 Receptor Blockers therapeutic use
Angiotensin-Converting Enzyme Inhibitors pharmacology
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Aortic Valve Stenosis drug therapy
Aortic Valve Stenosis genetics
Calcineurin biosynthesis
Calcineurin genetics
Cell Nucleus metabolism
Cytoplasm metabolism
Diuretics pharmacology
Diuretics therapeutic use
Estrogen Receptor alpha genetics
Estrogen Receptor beta genetics
Female
Gene Expression Regulation
Heart Ventricles metabolism
Hormone Replacement Therapy
Humans
Male
Microscopy, Fluorescence
Middle Aged
Natriuretic Peptide, Brain biosynthesis
Natriuretic Peptide, Brain genetics
Pressure
RNA, Messenger biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Aortic Valve Stenosis metabolism
Estrogen Receptor alpha biosynthesis
Estrogen Receptor beta biosynthesis
Up-Regulation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 110
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 15533858
- Full Text :
- https://doi.org/10.1161/01.CIR.0000147610.41984.E8