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Atherosclerosis. 2013 Oct;230(2):390-6. doi: 10.1016/j.atherosclerosis.2013.07.057. Epub 2013 Aug 23.

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

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  • 1Division of Geriatric Medicine, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: Kerrie.Moreau@UCDenver.edu.



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.


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-α 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-α contributes to impaired endothelial-dependent vasodilation and arterial stiffening in estrogen-deficient postmenopausal women.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.


Aging; Cardiovascular disease; Endothelium; Imaging; Inflammation; Menopause

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