Aldosterone receptor blockade inhibits degenerative processes in the early stage of calcific aortic stenosis.
Calcific aortic valve disease is associated with increased morbidity and mortality, especially in the elderly. To date, pharmacological therapies have not proven as effective as surgical intervention. Here, we used a hyperlipidemic rabbit model to investigate the potential effects of selective aldosterone inhibition on the early stages of aortic valve calcification, a pharmacological strategy that has not yet been tested. Forty New Zealand male rabbits fed a standard diet for 4 weeks were separated into three groups: (1) control (n=10), fed a standard diet; (2) vehicle (n=15), fed a hyperlipidemic diet (cholesterol 1%) plus vehicle; and (3) eplerenone (n=15), fed a hyperlipidemic diet plus 100 mg/kg/d eplerenone (last 4 weeks). After 8 weeks, animals were sacrificed and prepared aortic valve sections were examined with Von Kossa silver stain and by immunostaining for mineralocorticoid receptor, macrophages and angiotensin-converting enzyme. The presence of calcium deposits was confirmed by scanning electron microscopy. Eplerenone increased aldosterone levels but did not affect blood pressure, cholesterol or potassium levels. Hyperlipidemia induced macrophage accumulation and angiotensin-converting enzyme expression, as well as calcium deposition in the leaflets. All markers were decreased by eplerenone treatment. Immunohistochemistry for mineralocorticoid (aldosterone) receptors revealed similar expression in the leaflets of both control and hyperlipidemic groups. Collectively, these results indicate that aldosterone receptors are present in rabbit aortic valve leaflets and their selective blockade with eplerenone inhibits formation of the sclerotic lesions induced by a high fat diet.
Gkizas
Spyridon
S
Department of Anatomy, University of Patras, Patras, Greece. spyrosgizas@yahoo.com
Koumoundourou
Dimitra
D
Sirinian
Xara
X
Rokidi
Stamatina
S
Mavrilas
Dimosthenis
D
Koutsoukos
Petros
P
Papalois
Apostolos
A
Apostolakis
Efstratios
E
Alexopoulos
Dimitrios
D
Papadaki
Helen
H
D000818:Animals; D001018:Aortic Diseases / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D002114:Calcinosis / Q000150:complications*; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D000451:Mineralocorticoid Receptor Antagonists; D011817:Rabbits; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists