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Tumor necrosis factor-? inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.

ABSTRACT: Tumor necrosis factor (TNF)-?, a pleiotropic pro-inflammatory cytokine involved in a variety of biological processes including oxidative stress, has been associated with vascular dysfunction in aged and ovariectomized animals. We determined whether acute inhibition of TNF-? improves vascular endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.Arterial stiffness (carotid artery compliance) and endothelial function (brachial artery flow-mediated dilation [FMD]) were measured in postmenopausal women (n = 23; 57 ± 1 years, mean ± SE) before and following randomization to two days of either transdermal estradiol (0.05 mg/d, N = 12) or placebo (N = 11) alone and following a single subcutaneous injection of the TNF-? inhibitor, etanercept (25 mg), and in premenopausal (n = 9; 33 ± 2 years) before and following etanercept.Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than premenopausal women (P < 0.0001). In postmenopausal women, carotid artery compliance (n = 12; 0.59 ± 0.05-0.78 ± 0.06 mm(2)/mmHg × 10(-1), P < 0.001) and FMD (4.1 ± 0.6-6.0 ± 0.7%, P = 0.02) increased in response to estradiol but not placebo (n = 11). Carotid artery compliance (0.71 ± 0.06-0.81 ± 0.06 mm(2)/mmHg × 10(-1), P = 0.02) and FMD (5.2 ± 0.7-7.5 ± 0.9%, P = 0.003) increased with etanercept in the placebo group but had no effect in postmenopausal randomized to estradiol or premenopausal women. These results suggest that TNF-? contributes to impaired endothelial-dependent vasodilation and arterial stiffening in estrogen-deficient postmenopausal women.

SUBMITTER: Moreau KL

PROVIDER: S-EPMC3815590 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.

Moreau Kerrie L KL Deane Kevin D KD Meditz Amie L AL Kohrt Wendy M WM

Atherosclerosis 20130823 2

<h4>Objective</h4>Tumor necrosis factor (TNF)-α, a pleiotropic pro-inflammatory cytokine involved in a variety of biological processes including oxidative stress, has been associated with vascular dysfunction in aged and ovariectomized animals. We determined whether acute inhibition of TNF-α improves vascular endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.<h4>Methods</h4>Arterial stiffness (carotid artery compliance) and endothelial function (bra ...[more]

PMID: 24075772

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Project description:BackgroundEstrogens are recognized causal factors in breast cancer. Interindividual variation in estrogen metabolism may also influence the risk of breast cancer and could provide clues to mechanisms of breast carcinogenesis. Long-standing hypotheses about how estrogen metabolism might influence breast cancer have not been adequately evaluated in epidemiological studies because of the lack of accurate, reproducible, and high-throughput assays for estrogen metabolites.MethodsWe conducted a prospective case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants included 277 women who developed invasive breast cancer (case subjects) and 423 matched control subjects; at PLCO baseline, all subjects were aged 55-74 years, postmenopausal and not using hormone therapy, and provided a blood sample. Liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 15 estrogens and estrogen metabolites, in unconjugated and conjugated forms, including the parent estrogens, estrone and estradiol, and estrogen metabolites in pathways defined by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring. We calculated hazard ratios (HRs) approximating risk in highest vs lowest deciles of individual estrogens and estrogen metabolites, estrogens and estrogen metabolites grouped by metabolic pathways, and metabolic pathway ratios using multivariable Cox proportional hazards models. All statistical tests were two-sided.ResultsNearly all estrogens, estrogen metabolites, and metabolic pathway groups were associated with an increased risk of breast cancer; the serum concentration of unconjugated estradiol was strongly associated with the risk of breast cancer (HR = 2.07, 95% confidence interval [CI] = 1.19 to 3.62). No estrogen, estrogen metabolite, or metabolic pathway group remained statistically significantly associated with the risk of breast cancer after adjusting for unconjugated estradiol. The ratio of the 2-hydroxylation pathway to parent estrogens (HR = 0.66, 95% CI = 0.51 to 0.87) and the ratio of 4-hydroxylation pathway catechols to 4-hydroxylation pathway methylated catechols (HR = 1.34, 95% CI = 1.04 to 1.72) were statistically significantly associated with the risk of breast cancer and remained so after adjustment for unconjugated estradiol.ConclusionsMore extensive 2-hydroxylation of parent estrogens is associated with lower risk, and less extensive methylation of potentially genotoxic 4-hydroxylation pathway catechols is associated with higher risk of postmenopausal breast cancer.

Project description:Rheumatoid arthritis (RA) has been known to be associated with increased risk of cardiovascular disease (CVD). The aim of this study was to investigate the effects of Tai Chi exercise on CVD risk in elderly women with RA.In total, 56 female patients with RA were assigned to either a Tai Chi exercise group (29 patients) receiving a 3-month exercise intervention once a week or a control group (27 patients) receiving general information about the benefits of exercise. All participants were assessed at baseline and at 3 months for RA disease activity (Disease Activity Score 28 and Routine Assessment of Patient Index Data 3), functional disability (Health Assessment Questionnaire), CVD risk factors (blood pressure, lipids profile, body composition, and smoking), and three atherosclerotic measurements: carotid intima-media thickness, flow-mediated dilatation (FMD), and brachial-ankle pulse wave velocity (baPWV).FMD, representative of endothelial function, significantly increased in the Tai Chi exercise group (initial 5.85?±?2.05 versus 3 months 7.75?±?2.53%) compared with the control group (initial 6.31?±?2.12 versus 3 months 5.78?±?2.13%) (P?=?1.76?×?10(-3)). Moreover, baPWV, representative of arterial stiffness, significantly decreased in the Tai Chi exercise group (initial 1693.7?±?348.3 versus 3 months 1600.1?±?291.0 cm/s) compared with the control group (initial 1740.3?±?185.3 versus 3 months 1792.8?±?326.1 cm/s) (P?=?1.57?×?10(-2)). In addition, total cholesterol decreased significantly in the Tai Chi exercise group compared with the control group (-7.8?±?15.5 versus 2.9?±?12.2 mg/dl, P?=?2.72?×?10(-2)); other changes in RA-related characteristics were not significantly different between the two groups. Tai Chi exercise remained significantly associated with improved endothelial function (FMD; P?=?4.32?×?10(-3)) and arterial stiffness (baPWV; P?=?2.22?×?10(-2)) after adjustment for improvement in total cholesterol level.Tai Chi exercise improved endothelial dysfunction and arterial stiffness in elderly women with RA, suggesting that it can be a useful behavioral strategy for CVD prevention in patients with RA.

Dataset Information

Tumor necrosis factor-? inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.

Publications

Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.

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