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.
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.
Authors: P Gourdy; Z Mallat; C Castano; B Garmy-Susini; J L Mac Gregor; A Tedgui; J F Arnal; F Bayard Journal: Atherosclerosis Date: 2003-01 Impact factor: 5.162
Authors: F Squadrito; D Altavilla; G Squadrito; G M Campo; M Arlotta; V Arcoraci; L Minutoli; M Serrano; A Saitta; A P Caputi Journal: Eur J Pharmacol Date: 1997-09-24 Impact factor: 4.432
Authors: R Langenbach; S G Morham; H F Tiano; C D Loftin; B I Ghanayem; P C Chulada; J F Mahler; C A Lee; E H Goulding; K D Kluckman; H S Kim; O Smithies Journal: Cell Date: 1995-11-03 Impact factor: 41.582
Authors: Shimona Madalli; Martina Beyrau; James Whiteford; Johan Duchene; Inderpal Singh Nandhra; Nimesh S A Patel; Madhur P Motwani; Derek W Gilroy; Christoph Thiemermann; Sussan Nourshargh; Ramona S Scotland Journal: Biol Sex Differ Date: 2015-11-26 Impact factor: 5.027