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Arterioscler Thromb Vasc Biol. 2011 May;31(5):1075-83. doi: 10.1161/ATVBAHA.111.223545. Epub 2011 Feb 24.

Suppression of endothelial P-selectin expression contributes to reduced cell trafficking in females: an effect independent of NO and prostacyclin.

Author information

1
Department of Pharmacology, University College London, London, UK.

Abstract

OBJECTIVE:

Sex hormones underlie the lower incidence of cardiovascular disease in premenopausal women. Vascular inflammation is involved in the pathogenesis of several cardiovascular diseases and it has been reported that sex hormones modulate inflammatory responses but mechanisms responsible for these effects are not yet fully established. Herein, we assessed whether sex differences in leukocyte recruitment might exist and investigated the underlying mechanisms involved in this response.

METHODS AND RESULTS:

Treatment with interleukin-1β (IL-1β) or tumor necrosis factor-α caused leukocyte rolling, adhesion, and emigration in mesenteric postcapillary venules in vivo that was substantially reduced in female mice compared with male mice; this difference was abolished by ovariectomy and partially restored by estrogen replacement. Deletion of endothelial nitric oxide (NO) synthase or cyclooxygenase-1 alone or in combination did not alter the leukocyte recruitment in IL-1β-treated females but significantly enhanced this response in male mice. Treatment of murine pulmonary endothelial cells with IL-1β increased expression of P-selectin in male but not female cells.

CONCLUSIONS:

We have demonstrated a profound estrogen-dependent and NO and prostacyclin-independent suppression of leukocyte recruitment in females.

PMID:
21350195
PMCID:
PMC3501711
DOI:
10.1161/ATVBAHA.111.223545
[Indexed for MEDLINE]
Free PMC Article

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