Both estrogen receptor subtypes, alpha and beta, attenuate cardiovascular remodeling in aldosterone salt-treated rats.
Experimental and population-based studies indicate that female gender and estrogens protect the cardiovascular system against aldosterone-induced injury. Understanding the function of estrogens in heart disease requires more precise information on the role of both estrogen receptor (ER) subtypes, ERalpha and ERbeta. Therefore, we determined whether selective activation of ERalpha or of ERbeta would confer redundant, specific, or opposing effects on cardiovascular remodeling in aldosterone salt-treated rats. The ERalpha agonist 16alpha-LE2, the ERbeta agonist 8beta-VE2, and the nonselective estrogen receptor agonist 17beta-estradiol lowered elevated blood pressure, cardiac mass, and cardiac myocyte cross-sectional areas, as well as increased perivascular collagen accumulation and vascular osteopontin expression in ovariectomized rats receiving chronic aldosterone infusion plus a high-salt diet for 8 weeks. Uterus atrophy was prevented by 16alpha-LE2 and 17beta-estradiol but not by 8beta-VE2. Cardiac proteome analyses by 2D gel electrophoresis, mass spectrometry, and peptide sequencing identified specific subsets of proteins involved in cardiac contractility, energy metabolism, cellular stress response and extracellular matrix formation that were regulated in opposite directions by aldosterone salt treatment and by different estrogen receptor agonists. We conclude that activation of either ERalpha or ERbeta protects the cardiovascular system against the detrimental effects of aldosterone salt treatment and confers redundant, as well as specific, effects on cardiac protein expression. Nonfeminizing ERbeta agonists such as 8beta-VE2 have a therapeutic potential in the treatment of hypertensive heart disease.
Arias-Loza
Paula-Anahi
PA
Medizinische Klinik I, University of Würzburg, Würzburg, Germany.
Hu
Kai
K
Dienesch
Charlotte
C
Mehlich
Anna Maria
AM
König
Simone
S
Jazbutyte
Virginia
V
Neyses
Ludwig
L
Hegele-Hartung
Christa
C
Heinrich Fritzemeier
Karl
K
Pelzer
Theo
T
D000450:Aldosterone / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D047628:Estrogen Receptor alpha / Q000008:administration & dosage*; D047629:Estrogen Receptor beta / Q000008:administration & dosage*; D005260:Female; D007150:Immunohistochemistry; D010052:Ovariectomy; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D017673:Sodium Chloride, Dietary; D000450:Aldosterone