Upregulation of myocardial estrogen receptors in human aortic stenosis.
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.


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.


CONCLUSIONS
ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.
Nordmeyer
Johannes
J
Cardiovascular Disease in Women, Charite, Berlin, Germany.
Eder
Sarah
S
Mahmoodzadeh
Shokoufeh
S
Martus
Peter
P
Fielitz
Jens
J
Bass
Jan
J
Bethke
Nicole
N
Zurbrügg
Heinz R
HR
Pregla
Reinhard
R
Hetzer
Roland
R
Regitz-Zagrosek
Vera
V
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019703:Calcineurin / Q000096:biosynthesis / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D011312:Pressure; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D019703:Calcineurin