title: Sex-related differences in age-associated downregulation of human ventricular myocardial β1-adrenergic receptors.
abstract: BACKGROUND
  With increasing age, human ventricular myocardium exhibits selective downregulation of β1-adrenergic receptors (β1-ARs). We tested the hypothesis that sex differences exist in age-related changes in β1-ARs.
  
  
  METHODS
  Left (LV) and right (RV) ventricular tissue was obtained from 61 unplaceable potential organ donor hearts ages 1 to 71 years with no known cardiac history and from LVs removed from 56 transplant recipients with idiopathic dilated cardiomyopathy. β1-AR and β2-AR densities, the frequency of β1-AR389 gene variants, and β-AR function were determined.
  
  
  RESULTS
  Sex had a marked effect on the age-related decrease in β1-ARs. Female LVs had more pronounced downregulation (by 42% [p < 0.001] vs 22% [p = 0.21] in 31 male LVs) comparing the youngest (average age, 15.3 ± 5.5 years) to the oldest (average age, 50.8 ± 9.1 years) sub-groups. On regression analyses, female LVs exhibited a closer relationship between β1-AR density and age (r = -0.78, p <0.001 vs r = -0.46, p = 0.009 in males), with a second-degree polynomial yielding the best fit. There was no statistically significant relationship of β1-ARs to age in female or male idiopathic dilated cardiomyopathy LVs.
  
  
  CONCLUSIONS
  Sex affects age-related β-AR downregulation in normal human ventricles, with females exhibiting more profound decreases with increasing age. The curvilinear relationship between age and receptor density that plateaus around age 40 in women suggests an effect of sex hormones on β1-AR expression in the human heart.
authors.affiliation: Vanderbilt University, Nashville, Tennessee. Electronic address: joann.lindenfeld@vanderbilt.edu.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Lindenfeld
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cleveland
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: David P
authors.initials: DP
authors.lastname: Kao
authors.affiliation: The Montreal Heart Institute, Montreal, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Scott
authors.initials: S
authors.lastname: Wichman
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Jacques C
authors.initials: JC
authors.lastname: Bristow
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Valencia
authors.initials: V
authors.lastname: Peterson
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Juliana
authors.initials: J
authors.lastname: Rodegheri-Brito
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Armin
authors.initials: A
authors.lastname: Korst
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Penny
authors.initials: P
authors.lastname: Blain-Nelson
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: James
authors.initials: J
authors.lastname: Sederberg
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Hunt
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Gilbert
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Amrut V
authors.initials: AV
authors.lastname: Ambardekar
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Wayne
authors.initials: W
authors.lastname: Minobe
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Port
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D018342:Receptors, Adrenergic, beta-1
keywords: age; heart failure; left ventricle; sex differences; ventricular myocardium; β(1)-adrenergic receptors