Modulation of Circulating Cellular Adhesion Molecules in Postmenopausal Women With Coronary Artery Disease

Caulin–Glaser, Teresa; Farrell, William J.; Pfau, Steven; Zaret, Barry L.; Bunger, Katherine; Setaro, John F.; Brennan, Joseph; Bender, Jeffrey R.; Cleman, Michael; Cabin, Henry S.; Remetz, Michael S.

doi:10.1016/s0735-1097(98)00145-4

Cited by 106 publications

(55 citation statements)

References 26 publications

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“…For example, Cushman et al 13 found that estrogen only and estrogen/progestin therapy were both associated with an increase in CRP levels of Ն1 SD compared with baseline, and Caulin-Glauser et al 15 found that hormone replacement compared with no treatment was associated with a change in ICAM-1 levels of Ͼ3 SDs. Therefore, the present study was powered to detect even a relatively modest androgen-related change in inflammatory marker levels compared with effects previously observed in the sex steroid studies reported to date.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] In contrast, HRT reduces circulating levels of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin. [15][16][17][18] The effects of exogenous androgens on inflammatory markers have not been examined. We have previously shown that androgens increase endothelial VCAM-1 expression in vitro, 19 and we now report the effects of androgen treatment on serum inflammatory markers in healthy older men.…”

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confidence: 99%

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Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Liu

Williams

et al. 2002

ATVB

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Objective-Because male sex is an independent risk factor for the severity of atherosclerosis, it is possible that androgens may be proatherogenic. There is evidence that sex hormones, particularly estrogens, regulate (or modulate) inflammation, a process integral to atherogenesis. Because levels of serum inflammatory markers predict cardiovascular outcomes, we prospectively assessed the effects of androgen therapy on these markers in older men. Methods and Results-Levels of high-sensitivity C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured from sera collected at baseline and at the end of 2 randomized double-blind placebo-controlled trials evaluating the effects of 3 months of androgen treatment with either dihydrotestosterone (DHT) or recombinant human chorionic gonadotropin (rhCG) in healthy men aged Ͼ60 years with partial androgen deficiency (serum testosterone levels Ͻ15 nmol/L). For the DHT study (70 mg transdermally daily), 33 men completed 3 months of treatment (16 men were treated with DHT, and there were 17 controls). For the rhCG (250 g twice weekly) study, 20 men were treated with rhCG, and there were 20 controls. In both studies, groups were well matched for age and vascular risk factors. Androgen levels (DHT and testosterone) were consistently maintained at eugonadal levels throughout the trials, with estradiol markedly increased by rhCG but not DHT. Baseline CRP levels were 0.74 to 1.49 mg/L, sVCAM-1 levels were 847 to 950 ng/mL, and sICAM-1 levels were 256 to 292 ng/mL in all groups. Neither DHT nor rhCG resulted in significant changes in CRP, sVCAM-1, or sICAM-1 compared with placebo (PϾ0.3 in both studies). Conclusions-Exogenous androgen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women. These data provide a measure of reassurance concerning potential adverse cardiovascular effects of androgen therapy in older men.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Liu

Williams

et al. 2002

ATVB

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“…Recent publications point to an estrogen-related limitation of inflammatory responses in peripheral tissues 11,12 due to a decreased expression of adhesion molecules, including vascular cell adhesion molecule-1, E-selectin, and intercellular adhesion molecule-1. There is not, however, a clear consensus on whether estrogen acts directly or indirectly to decrease leukocyte adhesion.…”

Section: Discussionmentioning

confidence: 99%

Effects of Estrogen on Leukocyte Adhesion After Transient Forebrain Ischemia

Santizo

Anderson

et al. 2000

Stroke

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Background and Purpose-Recent findings indicate that estrogen (ie, 17␤-estradiol [E 2 ]) provides neuroprotection in models of transient global and focal ischemia. Enhanced postischemic leukocyte adhesion and infiltration have been linked to neuropathology in the brain as well as other tissues. We recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions. Methods-We compared leukocyte adhesion in pial venules in vivo in intact, ovariectomized (OVX), and E 2 -treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and hemorrhagic hypotension) and reperfusion. Adherent rhodamine-6G-labeled leukocytes were viewed through a closed cranial window with the use of intravital microscopy. Leukocyte adhesion was measured before ischemia and at different times after reperfusion. Results-Before ischemia, leukocyte adhesion (measured as a percentage of venular area occupied by adherent leukocytes) was 2 to 3 times greater in OVX versus intact or E 2 -treated OVX rats (7.0%, 3.4%, and 2.2%, respectively). This difference disappeared at 120 minutes of reperfusion, when comparable levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfusion (11.6% and 12.9%, respectively), while the other 2 groups showed significantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E 2 -treated OVX rats). Conclusions-Present

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“…Previous studies have suggested other potentially antiatherogenic effects of estrogen, including beneficial effects on the lipid profile, 6,7 coagulation factors, 12 cell adhesion molecule expression, 31,32 arterial plaque size, and cellular proliferation. 33 In an immortalized cell line that does not express estrogen receptors, supraphysiological doses of 17␤-estradiol have been shown to decrease lipid uptake by macrophages 25 ; however, the effects of physiological levels of estrogen and its antagonists on foam cell formation and the mechanism of lipoprotein uptake in female and male primary human macrophages have not been studied previously.…”

Section: Discussionmentioning

confidence: 99%

Estrogen and Progesterone Reduce Lipid Accumulation in Human Monocyte-Derived Macrophages

et al. 1999

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Background-Males have an earlier onset and greater prevalence of clinical atherosclerosis than age-matched females, which is consistent with an atheroprotective effect of the female sex steroids, estrogen and progesterone. We therefore examined the effects of estrogen and progesterone on human foam cell formation, a key early event in atherogenesis. Methods and Results-Monocytes from healthy female and male donors were obtained from white cell concentrates and allowed to differentiate into macrophages over 10 days. These human monocyte-derived macrophages (MDMs) were exposed to either control (0.1% vol/vol ethanol) or estrogen or progesterone treatment on days 3 through 10. Lipid loading was achieved on days 8 through 10 by incubation with acetylated LDL. Lipid from the MDMs was then extracted for analysis of cholesteryl ester (CE) content. 17␤-Estradiol at both physiological (2 nmol/L) and supraphysiological (20 and 200 nmol/L) concentrations produced a significant reduction in macrophage CE content (88Ϯ3%, 88Ϯ2%, and 85Ϯ4%, respectively; PϽ0.02 compared with control). Physiological and supraphysiological levels of progesterone (2, 10, and 200 nmol/L) produced an even more dramatic reduction in CE content (74Ϯ9%, 56Ϯ10%, and 65Ϯ8%, respectively; PϽ0.002 compared with control). This effect could be abrogated by coincubation with the progesterone receptor antagonist RU486. Neither estrogen nor progesterone produced a reduction in lipid loading in male-donor-derived MDMs. Detailed lipid trafficking studies demonstrated that both estrogen and progesterone altered macrophage uptake and/or processing of modified LDL. Conclusions-Physiological levels of estrogen and progesterone are associated with a female-sex-specific reduction in human macrophage lipid loading, which is consistent with an atheroprotective effect. (Circulation. 1999;100:2319-2325.)

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Modulation of Circulating Cellular Adhesion Molecules in Postmenopausal Women With Coronary Artery Disease

Abstract: A possible mechanism by which E2 exerts one of its cardioprotective effects is by limiting the inflammatory response to injury by modulating the expression of CAMs from the endothelium.

Cited by 106 publications

References 26 publications

Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Effects of Estrogen on Leukocyte Adhesion After Transient Forebrain Ischemia

Estrogen and Progesterone Reduce Lipid Accumulation in Human Monocyte-Derived Macrophages

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