Estrogen and progestagens differentially modulate vascular proinflammatory factors

Sunday, Lorraine; Tran, Minh Minh M; Krause, Diana N.; Duckles, Sue Piper

doi:10.1152/ajpendo.00550.2005

Cited by 76 publications

(62 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estrogenic abrogation of inflammation initiated by TNF-␣ is perhaps the most consistent of these effects and may be critical for linking infection to cardiovascular disease as TNF-␣ increases transiently even with low levels of lipopolysaccharide challenge (Jayachandran et al, 2007). Interestingly, in rats estrogen has been shown to suppress vascular inflammatory responses to IL-1␤ and lipopolysaccharide treatments, and this response has also been shown to vary through the estrous cycle (Galea et al, 2002;Ospina et al, 2004;Sunday et al, 2006). An intriguing result is that this anti-inflammatory effect of estrogen is lost in older female animals (Miller et al, 2004a;Sunday et al, 2007).…”

Section: A Inflammationmentioning

confidence: 99%

“…Thus, another possibility is that some of the various, little-studied estrogenic compounds in the CEE preparation were deleterious (Turgeon et al, 2004). Although animal studies have demonstrated untoward effects of medroxyprogesterone (Sunday et al, 2006), analysis of the CEEonly arm of the WHI appears to rule out this explanation (Barrett-Connor and Stuenkel, 1999;Turgeon et al, 2004;Hendrix et al, 2006). However, it is particularly notable that, in the Heart and Estrogen/Progestin Re-placement Study, only women with existing coronary disease were studied (Hulley et al, 1998), whereas in the WHI, the mean age of women at initial screening was 63 years, and more than 65% of the women were older than 60 years of age .…”

Section: Strokementioning

confidence: 99%

See 1 more Smart Citation

Vascular Actions of Estrogens: Functional Implications

2008

Self Cite

View full text Add to dashboard Cite

Section: A Inflammationmentioning

confidence: 99%

Section: Strokementioning

confidence: 99%

Vascular Actions of Estrogens: Functional Implications

2008

Self Cite

View full text Add to dashboard Cite

“…androgen; inflammation; vascular smooth muscle DESPITE THE GREATER INCIDENCE of stroke in men compared with age-matched premenopausal women (25a) and women's poorer outcomes following stroke (35), clinical studies regarding the effects of sex steroids on cerebral vascular pathophysiology remain a limited area of investigation. However, experimental research has shown that gonadal steroids modulate vascular inflammatory responses during pathological conditions (14,32,34,43). This is of great interest because the cerebral vasculature plays a central role in the pathogenesis of cardiovascular diseases, such as stroke (7), and in the initiation of inflammation after cerebral ischemia, which is a key determinant in stroke outcome (7,9).…”

mentioning

confidence: 99%

Dihydrotestosterone attenuates hypoxia inducible factor-1α and cyclooxygenase-2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation

Zuloaga

Gonzales

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Zuloaga KL, Gonzales RJ. Dihydrotestosterone attenuates hypoxia inducible factor-1␣ and cyclooxygenase-2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation. Am J Physiol Heart Circ Physiol 301: H1882-H1890, 2011. First published August 19, 2011 doi:10.1152/ajpheart.00446.2011 attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1␣ (HIF-1␣) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1␣ and COX-2 following hypoxia or hypoxia with glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1␣ levels were assessed via Western blot, and HIF-1␣ activation was indirectly measured via a DNA binding assay. Experiments were performed using cerebral arteries isolated from castrated male rats treated in vivo with placebo or DHT (18 days) followed by hypoxic exposure ex vivo (1% O 2), cerebral arteries isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100 nM; 18 h) and then exposed to hypoxia ex vivo (1% O 2), or primary human brain vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (cells 51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF-1␣. Following hypoxia or HGD, HIF-1␣ and COX-2 levels were increased; this response was blunted by DHT (cells HGD: Ϫ47% COX-2, Ϫ34% HIF-1␣; cells hypoxia: Ϫ29% COX-2, Ϫ54% HIF-1␣; arteries ex vivo: Ϫ37% COX-2; arteries in vivo: Ϫ35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced HIF-1␣ DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: Ϫ55%). These results demonstrate that upregulation of COX-2 and HIF-1␣ in response to hypoxia is suppressed by DHT via an androgen receptor-independent mechanism. androgen; inflammation; vascular smooth muscle DESPITE THE GREATER INCIDENCE of stroke in men compared with age-matched premenopausal women (25a) and women's poorer outcomes following stroke (35), clinical studies regarding the effects of sex steroids on cerebral vascular pathophysiology remain a limited area of investigation. However, experimental research has shown that gonadal steroids modulate vascular inflammatory responses during pathological conditions (14,32,34,43). This is of great interest because the cerebral vasculature plays a central role in the pathogenesis of cardiovascular diseases, such as stroke (7), and in the initiation of inflammation after cerebral ischemia, which is a key determinant in stroke outcome (7,9). Following ischemia, inflammation is initiated by cytokine-induced activation of transcription factors such as nuclear factor-B (NF-B) and hypoxiainducible factor 1-␣ (HIF-1␣), leading to increased production of proinflammatory mediators, such as inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) (2, 46). HIF-1␣ plays a particularly important role in cerebral ischemia because it is activated both by cytokines as a result of inflamm...

show abstract

“…with LPS (0.1 or 1 mg/kg) or saline. At 4 h after injection, when fever reached a plateau and induction of vascular inflammatory enzymes was maximal (Cao et al, 1995;Sunday et al, 2006), the aorta was excised, and aortic rings Fig. 1.…”

Section: Methodsmentioning

confidence: 99%

Raloxifene Elicits Combined Rapid Vasorelaxation and Long-Term Anti-Inflammatory Actions in Rat Aorta

Pinna

Bolego

Sanvito

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Previous studies reported the ability of raloxifene to acutely relax arterial and venous vessels, but the underlying mechanisms are controversial. Anti-inflammatory effects of the drug have been reported in nonvascular tissues. Therefore, the aim of this study was to investigate the nature of short-and longterm effects of raloxifene on selected aspects of vascular function in rat aorta. Isometric tension changes in response to raloxifene were recorded in aortic rings from ovariectomized female rats that underwent estrogen replacement, whereas long-term experiments were performed in isolated aortic smooth muscle cells (SMCs). Raloxifene (0.1 pM-0.1 M) induced acute vasorelaxation through endothelium-and nitric oxide (NO)-dependent, prostanoid-independent mechanisms. The relaxant response to raloxifene was significantly weaker than that to 17␤-estradiol and was sensitive to neither the nonselective estrogen receptor antagonist ICI 182,780 [7,4,5,5,sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol] nor a selective estrogen receptor (ER) ␣ antagonist. This rapid vasorelaxant effect was retained in aortic rings from rats treated with 0.1 mg/kg, but not 1 mg/kg, lipopolysaccharide, 4 h before sacrifice. In cultured aortic SMCs, raloxifene treatment (1 nM-1 M) for 24 h reduced inducible NO synthase activation in response to cytokines. This effect was prevented by the selective ER␣ antagonist and was associated with upregulation of ER␣ protein levels, which dropped markedly upon cytokine stimulation. These findings illustrate the relevance of classic ER-dependent pathways to the vascular anti-inflammatory effects rather than to the nongenomic vasorelaxation induced by raloxifene and may assist in the design of novel ER isoform-selective estrogen-receptor modulators targeted to the vascular system.Raloxifene is a selective estrogen-receptor modulator (SERM) approved for use in osteoporosis and has been suggested to be cardioprotective in women at high risk for coronary heart disease (Barrett-Connor et al., 2002), although these results were from post hoc analyses. In fact, the results of the recently completed RUTH (Raloxifene Use for The Heart) study indicate that treatment with raloxifene does not significantly affect the risk of coronary events in postmenopausal women at risk for coronary disease (Barrett-Connor et al., 2006). Thus, a more detailed understanding of raloxifene pharmacological action in vascular tissues is required to better define and unravel potential benefits of treatment with raloxifene and other SERMs.A certain number of studies have examined the direct effects of raloxifene on the vessel wall. It has been consistently shown that the drug acutely relaxes different arterial (Figtree et al., 1999;Tsang et al., 2004;Chan et al., 2005;Leung et al., 2005) and venous (Bracamonte et al., 2002;Chan et al., 2005) vessels from different animal species. A variety of underlying mechanisms, however, can be involved, including enhanced endothelial NO production (Figtree et al., 1999;Bracamonte et al., 200...

show abstract

Estrogen and progestagens differentially modulate vascular proinflammatory factors

Abstract: Duckles. Estrogen and progestagens differentially modulate vascular proinflammatory factors.

Cited by 76 publications

References 43 publications

Vascular Actions of Estrogens: Functional Implications

Vascular Actions of Estrogens: Functional Implications

Dihydrotestosterone attenuates hypoxia inducible factor-1α and cyclooxygenase-2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation

Raloxifene Elicits Combined Rapid Vasorelaxation and Long-Term Anti-Inflammatory Actions in Rat Aorta

Contact Info

Product

Resources

About