Sex-related differences in age-associated downregulation of human ventricular myocardial β₁-adrenergic receptors

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• 作者：JoAnn Lindenfeld ; MD^a ; ^{joann.lindenfeld@vanderbilt.edu" class="auth_mail" title="E-mail the corresponding author} ; Joseph C. Cleveland Jr ; MD^b ; David P. Kao ; MD^b ; Michel White ; MD^c ; Scott Wichman^b ; Jacques C. Bristow ; BA^b ; Valencia Peterson ; BS^b ; Juliana Rodegheri-Brito ; BS^b ; Armin Korst ; BS^b ; Penny Blain-Nelson ; MS^b ; James Sederberg ; MD^b ; Sharon A. Hunt ; MD^d ; E. Michael Gilbert ; MD^e ; Amrut V. Ambardekar ; MD^b ; Wayne Minobe ; BS^b ; Jonathan D. Port ; PhD^b ; Michael R. Bristow ; MD ; PhD^b
• 关键词：ventricular myocardium ; left ventricle ; sex differences ; β1-adrenergic receptors ; age ; heart failure
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：35
• 期：3
• 页码：352-361
• 全文大小：476 K

文摘

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.