Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells

Kikuchi, Noriko; Urabe, Mamoru; Iwasa, Kinuko; Okubo, Tomoharu; Hosoda, Tetsuya; Tazaki, Hiroshi; Honjo, Hideo

doi:10.1016/s0960-0760(99)00149-1

Cited by 27 publications

(20 citation statements)

References 31 publications

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“…Therefore, E2 was postulated to be produced from E1S and E1 in human VSMCs, and may exert direct effects on vessels in anti-atherogenesis, which is consistent with the result of a previous report. 25 The amount of STS was more abundant in female aorta with mild atherosclerotic changes than those with severe atherosclerotic changes. Therefore, in situ production of estrogens in VSMCs of female aorta via STS may possibly exert suppression of VSMC proliferation in the initial phase of atherosclerotic change.…”

Section: Discussionmentioning

confidence: 90%

“…26 This enzyme protein was also demonstrated in cultured human VSMCs. 25 After the conversion of E1S to E1 by STS, E1 was also converted to E2 ϫ 17␤-HSD-1. E1S was reported to be easily converted not only to E1, but also to E2.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24] In the human cardiovascular system, the expression of STS has been demonstrated in cultured VSMCs. 25 Moreover, mRNA and enzyme activity for both STS and EST have been demonstrated in the human aorta. 26 However, to date, the expression of these enzymes has not been examined in the human cardiovascular system with atherosclerosis.…”

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confidence: 99%

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Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Nakamura

Miki

Suzuki

et al. 2003

The American Journal of Pathology

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Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen. Therefore, we believe it is important to examine the status of estrogen metabolism in situ in the human cardiovascular system. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of estrogen-dependent human tissues and various sex steroid-dependent tumors. STS and EST, however, have not been studied in detail in the human vascular system associated with atherosclerotic changes. In the present study, we evaluated the relative abundance of STS-and ESTimmunoreactive protein and mRNA expression in human aorta using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity. STS expression levels were found to be significantly higher in the VSMCs obtained from female aortas with mild atherosclerotic changes than in those with severe atherosclerotic changes and in male aortas regardless of atherosclerotic changes. EST expression levels in the VSMCs of these aortas, however, were significantly higher in female aortas with severe atherosclerotic changes and in male aortas than in female aortas with mild atherosclerotic changes. We believe it is important to examine factors regulating the expression and activity of these estrogen-metabolizing enzymes in the human aorta. Various cytokines have been proposed to function as regulators of these enzymes in other tissues. In the present study, we studied the effects of interleukin (IL)-1␤, known to be produced in human atherosclerotic lesions, on the expression of these enzymes using cultured human VSMCs originally obtained from a female patient. IL-1␤ markedly inhibited the expression of STS mRNA and enzyme activity, but stimulated the expression of EST mRNA and enzyme activity. In addition, IL-1␤ also reduced E2 production from E1S and E1 in VSMCs.Results from the present study seem to suggest that the expression levels of both STS and EST mRNA and activity may be significantly associated with the degree of atherosclerotic changes in the female aorta, which may be related to cytokines produced in situ, such as IL-1␤, in human atherosclerotic lesions. Various epidemiological studies have reported a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause.1 Estrogen has, therefore, been proposed as a cardioprotective agent, especially in women.2 In ...

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Nakamura

Miki

Suzuki

et al. 2003

The American Journal of Pathology

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“…With respect to cytokine expression, estrogen in the high concentrations seen in pregnancy can inhibit proinflammatory pathways which include those activated by IL-1β (Polan et al, 1989), IL-6 (Keck et al, 1998, Kikuchi et al, 2000, IL-8 (Rodriguez et al, 2002) and TNF-α (Rogers and Eastell, 2001) as well as inhibiting the activity of natural killer cells (Seaman and Gindhart, 1979). In contrast, the secretion of 'anti-inflammatory interleukins' IL-4 (Kamada et al, 2001), IL-10 (Kanda and Tamaki, 1999) and transforming growth factor (TGF)-β (Hatthachote and Gillespie, 1999) are stimulated by estrogen in these high levels.…”

Section: Page 13 Of 24mentioning

confidence: 99%

Endocrine immune interactions in human parturition

Golightly

Jabbour

Norman

2011

Molecular and Cellular Endocrinology

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Human parturition is an inflammatory event, modulated and influenced by a host of other environmental and physiological processes, including the endocrine hormones.Complex bidirectional communication occurs between the two systems to bring about some of the changes that are seen in labour, an event that is not yet fully understood.Preterm birth is a major problem in obstetrics and neonatology, with dysfunctional labour or prolonged pregnancy also making increasingly significant contributions to maternal morbidity. With better understanding of normal and abnormal parturition we may be able to develop novel ways of treating these complications of pregnancy and reduce maternal and neonatal morbidity and mortality. This review discusses the crucial role that endocrine-immune interaction plays in the process of labour and in the processes of abnormal and preterm labour. We propose that amongst these complex interactions it is the immune system that is the driving force behind human parturition. Keywords Parturition Endocrine InflammationImmune

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“…E 3 is considered a "weak estrogen" and is widely used in Japan because it has similar beneficial effects as E 2 in menopausal women for prevention of osteoporosis and atherosclerotic disease, without endometrial proliferation [35]. Although less studied, E 3 has been shown to suppress inflammatory cytokines in vascular smooth muscle and decrease atheromas in high cholesterol-fed rabbits [24,25]. In addition, E 3 was shown to be as protective as E 2 of cardiac lesions in spontaneously hypertensive strokeprone rats [18].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

Cipolla¹,

Godfrey²,

Wiegman³

2009

UMIC

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Objective-We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability.Methods-Female ovariectomized Sprague Dawley rats were replaced with estradiol (E 2 ) and estriol (E 3 ) (OVX+E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries.Results-Ovariectomy increased myogenic tone in PA compared to CTL that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX+E was 44 ± 3% vs. 51 ± 1% and 54 ± 3% (p<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals, however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX and OVX+E was (ng/mL): 3.4 ± 1.2, 20.2 ± 5.3 (p<0.01 vs. CTL) and 6.15 ± 1.2 (n.s.).Conclusions-These results suggest that estrogen replacement may not be beneficial for small vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it.

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Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells

Cited by 27 publications

References 31 publications

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Endocrine immune interactions in human parturition

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

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