Sex-related differences in age-associated downregulation of human ventricular myocardial ß1-adrenergic receptors.

BACKGROUND: With increasing age, human ventricular myocardium exhibits selective downregulation of ß1-adrenergic receptors (ß1-ARs). We tested the hypothesis that sex differences exist in age-related changes in ß1-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. ß1-AR and ß2-AR densities, the frequency of ß1-AR389 gene variants, and ß-AR function were determined. RESULTS: Sex had a marked effect on the age-related decrease in ß1-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 ß1-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 ß1-ARs to age in female or male idiopathic dilated cardiomyopathy LVs. CONCLUSIONS: Sex affects age-related ß-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 ß1-AR expression in the human heart.

Comparison of multiple psychological distress measures between men and women preparing for in vitro fertilization.

OBJECTIVE: To compare multiple measures of psychological distress between men and women preparing for IVF. DESIGN: Retrospective cohort study. SETTING: Outpatient, academic infertility clinic. PATIENT(S): One hundred sixty-two consecutive couples presenting for infertility treatment with IVF. INTERVENTION(S): Measures were completed as part of a routine, infertility-focused psychological evaluation, including the Beck Depression Inventory, State-Trait Anxiety Inventory, State-Trait Anger Inventory, and Impact of Events Scale. MAIN OUTCOME MEASURE(S): Scores of above psychological questionnaires. RESULT(S): Psychological distress scores were statistically significantly higher among women than men for symptoms of depression, state anxiety, infertility specific distress, and general perceived stress. However, aside from infertility-specific distress (d = .43), effect sizes for the paired differences between females and males ranged from d = .18 to .23. CONCLUSION(S): Women consistently scored higher on multiple measures of psychological distress than their male partners in the context of preparing for IVF. Comparison of infertility-specific distress scores yielded the largest statistically and clinically significant difference compared with traditional measures of general depression and anxiety symptoms.

Reciprocal modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium.

BACKGROUND: Mitogen-activated protein kinases (MAPKs), consisting of the ERK1/2, JNKs, and p38-kinase families, play a key role in the regulation of myocyte growth and apoptosis in vitro. The activity of MAPKs is regulated by dual-specificity MAPK phosphatases (MKPs). Because myocardial failure is associated with myocyte hypertrophy and apoptosis, MAPKs may play a pathophysiologic role in human myocardial failure. METHODS AND RESULTS: We measured MAPKs activities and the protein levels of MAPKs and MKPs (MKP-1 and MKP-2) in the myocardium explanted at the time of transplantation from patients with end-stage failure caused by idiopathic dilated cardiomyopathy (n = 5-7). Nonfailing donor hearts (n = 5-7) were used for comparison. Although the protein levels for JNK1/2 and p38-kinase in failing hearts were not different from levels in nonfailing hearts, the activities of both were decreased (P <.05). Despite a >3-fold increase in the protein level for ERK1/2 in failing hearts, ERK1/2 activity was not increased. Expression of MKP-2 was significantly increased in failing hearts, while expression of MKP-1 was increased in 5 of 7 failing hearts as measured by Western analysis. CONCLUSIONS: JNK1/2 and p38 activities are decreased in failing human myocardium. Increased expression of MKPs may therefore contribute to decreased MAPKs activity in failing human myocardium.