-
[show abstract]
[hide abstract]
ABSTRACT: Vascular endothelium expresses both the estrogen receptors (ERs) α and β, and ERα mediates development of early atherosclerosis in male mice. This process is thought to be testosterone-dependent. We hypothesized that male murine aortic endothelium produces robust levels of estradiol by aromatase conversion of testosterone, and that regulation of this process is mediated by the presence of ERs, primarily ERα. Aortic endothelium was isolated from ERα knockout (ERα -/-) and wild-type (ERα +/+) male mice and treated with testosterone or the 5α reduction product dihydrotestosterone (DHT), with or without the P450 aromatase inhibitor anastrazole, or a non-specific estrogen receptor antagonist. Aromatase gene expression and estradiol production were assayed. Treatment with testosterone, but not DHT, caused increased aromatase expression and estradiol production in ERα +/+ endothelium that was attenuated by disruption of ERα in the ERα -/- group. Anastrazole inhibition of aromatase reduced testosterone-induced aromatase expression and estradiol levels in both ERα -/- and ERα +/+ endothelium. Antagonism of both ERs decreased testosterone-induced aromatase expression in both wild-type and knockout groups. The effects of the receptor antagonist on estradiol production differed between the two groups, however, with a reduction in estradiol release from the ERα +/+ cells and complete abolition of estradiol release from the ERα -/- cells. Thus, estradiol production in vascular endothelium from male mice is robust, depends on the aromatic conversion of testosterone and requires functional ERα to achieve maximal levels of estradiol generation. Local vascular production of aromatase-mediated estradiol in response to circulating testosterone may affect ERα-dependent mechanisms to increase susceptibility to early atheroma formation in male mice. This pathway may have important therapeutic relevance for reducing the risk of atherosclerotic cardiovascular disease in human males.
SpringerPlus. 12/2013; 2(1):214.
-
[show abstract]
[hide abstract]
ABSTRACT: The challenges of balancing a career and family life disproportionately affect women in academic health sciences and medicine, contributing to their slower career advancement and/or their attrition from academia. In this article, the authors first describe their experiences at the University of California, Davis, School of Medicine developing and implementing an innovative accelerator intervention designed to promote faculty work-life balance by improving knowledge, awareness, and access to comprehensive flexible career policies. They then summarize the results of two faculty surveys-one conducted before the implementation of their intervention and the second conducted one year into their three-year intervention-designed to assess faculty's use and intention to use the flexible career policies, their awareness of available options, barriers to their use of the policies, and their career satisfaction. The authors found that the intervention significantly increased awareness of the policies and attendance at related educational activities, improved attitudes toward the policies, and decreased perceived barriers to use. These results, however, were most pronounced for female faculty and faculty under the age of 50. The authors next discuss areas for future research on faculty use of flexible career policies and offer recommendations for other institutions of higher education-not just those in academic medicine-interested in implementing a similar intervention. They conclude that having flexible career policies alone is not enough to stem the attrition of female faculty. Such policies must be fully integrated into an institution's culture such that faculty are both aware of them and willing to use them.
Academic medicine: journal of the Association of American Medical Colleges 04/2013; · 2.34 Impact Factor
-
The American journal of medicine 07/2012; 125(7):719-28. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although women receive nearly half of all doctoral degrees and show a high interest in academic careers, the pipeline is leaky. The challenge of balancing life course events with career trajectory is an important determinant leading to premature dropout or slower career advancement. This report describes the findings of the first phase of a National Institute of Health Office of Research on Women's Health (NIH ORWH)-funded study using survey and academic data for exploring satisfaction and awareness of/intent to use specific career flexibility options at the University of California, Davis (UCD).
All men and women faculty in the UCD's Schools of Medicine (SOM) and Veterinary Medicine (SVM) and College of Biological Science (CBS) were surveyed. Data also were obtained from deans' offices on use of family-friendly benefits by faculty.
Three hundred twenty-five total survey responses were received from the SOM, 83 from SVM, and 64 from CBS, representing 42%, 46%, and 52% of their total faculty, respectively. In each school, large percentages of men (32%-60%) and women (46%-53%) faculty have children under 18 and a moderately high level of demand of family care responsibilities. Women were significantly more likely to be childless, particularly in the SOM (35% vs. 14%, p<0.001). For all schools, documented use of any family-friendly policy was low (0%-11.5%), as was awareness of policies, although both were significantly higher for women than for men. Significantly more women than men wanted to use policies or chose not to, particularly in the SOM (51% vs. 28%, p<0.001, and 37% vs. 23%, p=0.016, respectively), because of multiple barriers. Faculty in all schools agreed/highly agreed that policies were important to recruitment, retention, and career advancement.
Family-friendly policies are pertinent to men and women, as both demonstrate interest and need, linked to increased career satisfaction. A family-friendly policy is important, particularly for women in the biomedical sciences.
Journal of Women s Health 08/2011; 20(10):1485-96. · 1.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background: The diversity of the U.S. population and disparities in the burden of cardiovascular disease (CVD) require that public health education strategies must target women and racial/ethnic minority groups to reduce their CVD risk factors, particularly in high-risk communities, such as women with the metabolic syndrome (MS). Methods: The data reported here were based on a cross-sectional face-to-face survey of women recruited from four participating sites as part of the national intervention program, Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Care in High-Risk Women. Measures included baseline characteristics, sociodemographics, CVD related-knowledge and awareness, and Framingham risk score (FRS). Results: There were 443 of 698 women (63.5%) with one or more risk factors for the MS: non-Hispanic white (NHW), 51.5%; non-Hispanic black (NHB), 21.0%; Hispanic, 22.6%. Greater frequencies of MS occurred among Hispanic women (p<0.0001), those with less than a high school education (70.0%) (p<0.0001), Medicaid recipients (57.8%) (p<0.0001), and urbanites (43.3%) (p<0.001). Fewer participants with MS (62.6%) knew the leading cause of death compared to those without MS (72.1%) (p<0.0001). MS was associated with a lack of knowledge of the composite of knowing the symptoms of a heart attack plus the need to call 911 (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-0.97, p=0.04). Conclusions: Current strategies to decrease CVD risk are built on educating the public about traditional factors, including hypertension, smoking, and elevated low-density lipoprotein cholesterol (LDL-C). An opportunity to broaden the scope for risk reduction among women with cardiometabolic risk derives from the observation that women with the MS have lower knowledge about CVD as the leading cause of death, the symptoms of a heart attack, and the ideal option for managing a CVD emergency.
Journal of Women s Health 06/2011; 20(6):893-900. · 1.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Maternal mainstream tobacco smoking is known to have adverse outcomes on fetal respiratory function; however, no data is currently available on the effects of passive exposure to tobacco smoking and environmental tobacco smoke (ETS) on fetal systemic arterial structure and function. Eight pregnant rhesus macaque monkeys were studied at the California Regional Primate Research Center breeding colony. The estimated gestational age for each dam was established by sonography performed before gestational day 40. Two inhalation chambers were used, each with an air capacity of 3.5 m(3), and each housed two dams. Aged and diluted sidestream smoke was used as a surrogate for ETS. Exposure to ETS (1 mg/m(3)) occurred for 6 h/day, 5 days/week, beginning on gestational day 100. All dams were allowed to give birth spontaneously and then ETS exposure continued 70-80 days postnatally with the chamber containing both the mother and infant. Carotid arteries from four control (C) and four ETS-treated newborns were analyzed for mRNA by gene macroarray and for protein by Western blotting. A total of 588 cardiovascular genes were studied. Four genes were upregulated by ETS compared to C, and nine genes were downregulated (≥2-fold change). Three genes were selected for further study. Following ETS exposure, neonatal carotid arteries of non-human primates manifested evidence of inflammation with increased gene and protein expression of LFA-1 and RANTES, proteins that are recognized to be important in vascular adhesion and inflammation, and downregulation of expression for the receptor for VEGF, which has a key role in angiogenesis. Prenatal and postnatal exposure to ETS increases expression of pro-inflammatory genes and may be responsible for early arterial vascular remodeling that is predisposing to a subsequent vascular disease.
Journal of Cardiovascular Translational Research 10/2010; 3(6):696-703. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: CVD (cardiovascular disease) is the leading cause of death for women. Considerable progress has been made in both our understanding of the complexities governing menopausal hormone therapy and our understanding of the cellular and molecular mechanisms underlying hormone and hormone receptor function. Understanding the interplay of atherosclerosis and sex steroid hormones and their cognate receptors at the level of the vessel wall has important ramifications for clinical practice. In the present review, we discuss the epidemiology of CVD in men and women, the clinical impact of sex hormones on CVD, and summarize our current understanding of the pathogenesis of atherosclerosis with a focus on gender differences in CVD, its clinical presentation and course, and pathobiology. The critical animal and human data that pertain to the role of oestrogens, androgens and progestins on the vessel wall is also reviewed, with particular attention to the actions of sex hormones on each of the three key cell types involved in atherogenesis: the endothelium, smooth muscle cells and macrophages. Where relevant, the systemic (metabolic) effects of sex hormones that influence atherogenesis, such as those involving vascular reactivity, inflammation and lipoprotein metabolism, are discussed. In addition, four key current concepts in the field are explored: (i) total hormone exposure time and coronary heart disease risk; (ii) the importance of tissue specificity of sex steroid hormones, critical timing and the stage of atherosclerosis in hormone action; (iii) biomarkers for atherosclerosis with regard to hormone therapy; and (iv) the complex role of sex steroids in inflammation. Future studies in this field will contribute to guiding clinical treatment recommendations for women and help define research priorities.
Clinical Science 09/2010; 119(12):493-513. · 4.61 Impact Factor
-
Amparo C Villablanca,
Laurel A Beckett,
Yueju Li,
Shantelle Leatherwood,
Santosh K Gill,
Elsa-Grace V Giardina,
Anne L Taylor,
Carol Barron,
JoAnne M Foody,
Suzanne Haynes,
Gail D'Onofrio
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to improve the fund of knowledge, reduce cardiovascular disease (CVD) risk, and attain Healthy People 2010 objectives among women in model women's heart programs.
A 6-month pre/post-longitudinal educational intervention of high-risk women (n = 1310) patients at six U.S. women's heart programs consisted of comprehensive heart health counseling and use of American Heart Association/American College of Cardiology (AHA/ACC) Evidence-Based Guidelines as enhancement to usual care delivered via five integrated components: education/awareness, screening/risk assessment, diagnostic testing/treatment, lifestyle modification/rehabilitation, and tracking/evaluation. Demographics, before and after knowledge surveys, clinical diagnoses, laboratory parameters, and Framingham risk scores were also determined. Changes in fund of knowledge, awareness, and risk reduction outcomes and Healthy People 2010 objectives were determined.
At 6 months, there were statistically significant improvements in fund of knowledge, risk awareness, and clinical outcomes. Participants attained or exceeded >90% of the Healthy People 2010 objectives. Proportions of participants showing increased knowledge and awareness of CVD as the leading killer of women, of all signs and symptoms of a heart attack, and calling 911 increased significantly (11.1%, 25.4%, and 34.6%, respectively). Health behavior counseling for physical activity, diet, and diabetes as CVD risk factors increased significantly (28.3%, 28.2%, and 12.5%, respectively). There was a statistical 4.1% increase in participants with systolic blood pressure (SBP) <140/90 mm Hg, a 4.7% decrease in participants with total cholesterol (TC) >240 mg/dL, a 4.5% decrease in participants with TC >200 mg/dL, a 5.9% decrease in participants with high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, a 4.4% decrease in participants with HDL-C <40 mg/dL, and an 8.8% increase in diabetics with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL.
CVD prevention built around a comprehensive heart care model program and AHA/ACC Evidence-Based Guidelines can be successful in improving knowledge and awareness, CVD risk factor reduction, and attainment of Healthy People 2010 objectives in high-risk women. Thus, these programs could have a dramatic and lasting impact on the health of women.
Journal of Women s Health 07/2010; 19(7):1313-25. · 1.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Health Care Programs for High Risk Women has funded six diverse centers to provide chronic disease risk factor screening and lifestyle interventions for women and focuses specifically on low-income, minority women.
This article describes the rationale for these diverse programs across the country, all focusing on improving outcomes for women with or at risk for cardiovascular disease (CVD). The six programs include College of Physicians and Surgeons at Columbia University, Christ Community Health Services in Memphis, Women's Heart Center of Fox Valley Cardiovascular Consultants, University of Minnesota, University of California Davis Women's Cardiovascular Medicine Program, and Yale-New Haven Hospital's Women's Heart Advantage.
We present six differing approaches to women's heart programs. Based on this experience, promoting CVD prevention in women is a feasible healthcare delivery strategy for health promotion and for delivering preventive strategies for high-risk women. It is possible to deliver heart-healthy programs through existing healthcare infrastructures. These programs provide important models for public health, voluntary, and other health organizations to develop networks for population-based, targeted, relatively low cost programs that support Healthy People 2010 objectives for lifestyle changes and cardiovascular health. Ongoing longitudinal analysis of the programs will provide information about clinical outcomes and sustainability of such programs beyond the funding period.
Journal of Women s Health 02/2010; 19(3):507-16. · 1.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiovascular disease is the leading cause of death in postmenopausal women. While diet and lifestyle remain the cornerstones of prevention, a low-fat/high-carbohydrate diet is associated with hyperglycemia and hyperlipemia-atherosclerotic risk factors affected by postprandial conditions. The objective of this study was to examine the acute response of lipids and insulin to a low-fat/high-carbohydrate meal with either a high-glycemic or a low-glycemic index in healthy postmenopausal women. Fifteen healthy postmenopausal women were enrolled in a randomized crossover dietary intervention study. Levels of glucose, triglyceride, free fatty acids (FFAs), and insulin were measured preprandially and for 240 minutes after consumption of the test meals. In response to the high-glycemic compared with the low-glycemic index meal, postprandial insulin levels had a higher peak (65.4 vs 48.1 microU/mL, respectively), the homeostasis model assessment-insulin resistance (HOMA-IR) was significantly higher (P=.014), serum triglyceride levels declined significantly (P<.001), and there was a small reduction in FFA levels, although the difference did not reach statistical significance. The results suggest a postprandial impact of glycemic index on cardiovascular metabolic biomarkers in postmenopausal women and may have implications for dietary glycemic modification of cardiovascular risk in women.
Preventive Cardiology 01/2010; 13(1):29-35.
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to reduce cardiovascular disease (CVD) risk in women by implementing a cardiovascular prevention health promotion program in faith- and community-based sites. The primary outcomes were reducing obesity and increasing physical activity. A longitudinal cohort of high-risk (age > 40, ethnic minority) women (n = 1,052) was enrolled at 32 sites across the USA. The pre- or post-educational intervention consisted of eight biweekly counseling sessions conducted over 4 months each addressing one of six of the major CVD risk factors (smoking, diabetes, hypertension, cholesterol, obesity, and physical inactivity) as well as signs and symptoms of a heart attack and stroke; plus 4-6 maintenance sessions over three additional months. A multifaceted approach delivered by lay and medically trained personnel involving medical screenings, health behavior counseling, risk behavior modification, and stage of change were determined at baseline and end of counseling or maintenance. Following list-wise deletion, data were analyzed on 423 women who completed all follow-up time-points. Overall, significant improvement was attained in most of 28 secondary outcomes but not in the primary outcomes. Knowledge and awareness of heart disease as the leading killer or women, all of the signs and symptoms of a heart attack, calling 911, and CVD risk factors increased significantly (p < 0.05) by 8.8%, 13.6%, 5.8%, and 10%, respectively. There was a 10% (p < 0.05) increase in participants attaining control for hypertension (blood pressure < 140/90) coupled with a significant reduction in mean blood pressure in the entire cohort. Knowledge of effective CVD risk modification strategies for all CVD risk factors increased significantly (p < 0.05), except for obesity. In addition, there were significant (p < 0.05) increases in forward movement in stage of change for each CVD risk factor (range +10% to +39%). Thus, a heart disease prevention intervention built around a model of community engagement, advocacy, self-efficacy, resource knowledge, and health promotion in faith- and community-based organizations is successful at improving cardiovascular knowledge and awareness outcomes in high-risk women. Limitations of our study include the high dropout rate, significant time demands on site coordinators, limited resources for program implementation, lack of morbidity and mortality endpoints, and failure to attain the primary outcomes of weight loss and physical activity. Future studies should not only assess the effect of community education interventions on lifestyle change and knowledge and awareness of participants but should also address program duration, cost, and resources required to attain improved outcomes.
Journal of Cardiovascular Translational Research 09/2009; 2(3):306-20. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Estrogen is atheroprotective and a high-affinity ligand for both known estrogen receptors, ERalpha and ERbeta. However, the role of the ERalpha in early-stage atherosclerosis has not been directly investigated and is incompletely understood. ERalpha-deficient (ERalpha-/-) and wild-type (ERalpha+/+) female mice consuming an atherogenic diet were studied concurrent with estrogen replacement to distinguish the actions of 17beta-estradiol (E(2)) from those of ERalpha on the development of early atherosclerotic lesions. Mice were ovariectomized and implanted with subcutaneous slow-release pellets designed to deliver 6 or 8 mug/day of exogenous 17beta-estradiol (E(2)) for a period of up to 4 months. Ovariectomized mice (OVX) with placebo pellets (E(2)-deficient controls) were compared to mice with endogenous E(2) (intact ovaries) and exogenous E(2). Aortas were analyzed for lesion area, number, and distribution. Lipid and hormone levels were also determined. Compared to OVX, early lesion development was significantly (p < 0.001) attenuated by E(2) with 55-64% reduction in lesion area by endogenous E(2) and >90% reduction by exogenous E(2). Compared to OVX, a decline in lesion number (2- to 4-fold) and lesser predilection (~4-fold) of lesion formation in the proximal aorta also occurred with E(2). Lesion size, development, number, and distribution inversely correlated with circulating plasma E(2) levels. However, atheroprotection was independent of ERalpha status, and E(2) athero-protection in both genotypes was not explained by changes in plasma lipid levels (total cholesterol, triglyceride, and high-density lipoprotein cholesterol). The ERalpha is not essential for endogenous/exogenous E(2)-mediated protection against early-stage atherosclerosis. These observations have potentially significant implications for understanding the molecular and cellular mechanisms and timing of estrogen action in different estrogen receptor (ER) deletion murine models of atherosclerosis, as well as implications to human studies of ER polymorphisms and lipid metabolism. Our findings may contribute to future improved clinical decision-making concerning the use of hormone therapy.
Journal of Cardiovascular Translational Research 09/2009; 2(3):289-99. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Activation of the estrogen receptor-alpha (ERalpha) mediates the vasculoprotective effects of estrogen, in part, through modulating nitric oxide (NO) production and vasodilation. Whereas inflammation is accompanied by altered vascular reactivity and underlies the pathogenesis of vascular disease, the role of the ERalpha in the vascular responses associated with acute systemic inflammation remains poorly characterized. Contractile and relaxation responses of isolated aortic segments were investigated 12 h after ip injection of saline or lipopolysaccharide (LPS, 10 mg/kg) in male wild-type (ERalpha(+/+)) and ERalpha-deficient (ERalpha(-/-)) mice. As previously observed, LPS-injected ERalpha(+/+) mice displayed reduced contractile responses to phenylephrine and enhanced vasodilation in response to acetylcholine. In contrast, aortic tissues from LPS-injected ERalpha(-/-) mice displayed enhanced contractile responses and reduced sensitivity to acetylcholine- and sodium nitroprusside-induced vasodilation. LPS treatment in ERalpha(+/+) and ERalpha(-/-) mice resulted in similar increased levels of systemic NO production and inducible NO synthase expression in the vascular wall. However, expression of mRNA and protein for endothelial NOS and soluble guanylate cyclase (alpha- and beta-subunits) were significantly reduced in aortic tissues from LPS-treated ERalpha(-/-) animals, possibly accounting for reduced endothelial NO production and reduced smooth muscle responses to NO. These findings represent new evidence of the functional role of ERalpha in the male vasculature and suggest that during acute LPS-induced inflammatory responses, the ERalpha mediates the sustained expression of the molecular machinery essential for endothelial NO synthesis (i.e. endothelial NOS) and the vascular responses to NO (i.e. soluble guanylate cyclase).
Endocrinology 04/2007; 148(3):1403-11. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The overall goal of this project was to examine the interactions of hyperglycemia and loss of ovarian hormones on the artery wall in a type I diabetic mouse model. Intact or ovariectomized (OVX) female BALB/C mice were fed a high-cholesterol diet. Half the animals were treated with steptozotocin to induce insulin-deficient diabetes mellitus, generating four treatment groups: control, intact; control, ovariectomized; diabetic, intact; diabetic, ovariectomized (DOVX). We examined arterial structure and function and found that 1) diabetes and ovariectomy additively increased endothelial layer permeability, 2) arterial stiffening was increased in DOVX, 3) DOVX synergistically increased atheroma formation, and 4) ultrastructural evaluation revealed that the basal lamina was often multilayered and formed convoluted aggregates separating endothelium from the internal elastic lamina in diabetic, but not control arteries or arteries from OVX mice. Endothelium overlying these regions formed thin cytoplasmic extensions between these aggregates and was often separated from the basal lamina by electron lucent spaces. Our studies showed that diabetes and loss of ovarian function have additive and synergistic effects to worsen arterial pathophysiology by disrupting the arterial endothelial layer with increased permeability and increased atheroma formation.
AJP Regulatory Integrative and Comparative Physiology 03/2007; 292(2):R723-30. · 3.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (P<0.05 vs. baseline) after the 6-week cocoa intervention in the high CF group, compared with 32% in the low CF cocoa group (P=ns vs. baseline). The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated (r2=0.8) with a significant decrease (11%) in plasma levels of soluble vascular cell adhesion molecule-1. Similar responses were not observed after chronic use of low CF. There were no significant differences between high and low CF in other biochemical markers and parameters measured. This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity.
Journal of Cardiovascular Pharmacology 02/2006; 47 Suppl 2:S177-86; discussion S206-9. · 2.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiovascular disease is the leading cause of death among men and women in Western societies. Over the past decade, interest in a better understanding of gender differences in cardiovascular disease has heightened. Concomitantly, the use of hormone therapy for cardiovascular risk reduction in postmenopausal women has come into question in light of recent landmark clinical studies casting doubt on the benefits of this therapy. As a consequence, alternatives to conventional hormone replacement, including selective estrogen receptor modulators and phytoestrogens, have attracted considerable attention. The authors provide an up-to-date review of the clinical actions of selective estrogen receptor modulators on cardiovascular disease. The actions of tamoxifen, raloxifene, droloxifene, and soy phytoestrogens are discussed in the context of cardiovascular disease epidemiology, coronary events, clinical markers of cardiovascular risk, and vascular function. In addition, the authors' current understanding of the mechanism of action of these agents is discussed and recommendations for clinical practice are reviewed.
Preventive Cardiology 02/2004; 7(2):73-9.
-
[show abstract]
[hide abstract]
ABSTRACT: Controversy exists about the ability of soy protein and isoflavones to modulate vascular reactivity and biochemical cardiovascular disease risk markers in healthy, normolipidemic postmenopausal women.
The objective was to investigate whether the consumption of soy protein with isoflavones would result in improved vascular reactivity and decreased biochemical markers of endothelial dysfunction and inflammation, independent of enhanced lipid and antioxidant effects.
Healthy postmenopausal women (n = 28) were enrolled in a randomized, double-blind, crossover study, and they consumed 25 g of 3 protein products/d for 6 wk each, with intervening washout periods. The products were isolated soy protein with isoflavones, ethanol-washed isolated soy protein with trace isoflavones, and total milk protein, which supplied 107, 2, and 0 mg total isoflavone (aglycone) units/d, respectively. We studied vascular function by using brachial artery reactivity values, plasma concentrations of vasoactive factors, endothelial inflammatory markers, and plasma isoflavone concentrations. The resistance of whole plasma and isolated LDL to copper-mediated oxidation was measured by conjugated diene formation.
Postocclusion peak flow velocity of the brachial artery was significantly (P = 0.03) lower after treatment with isolated soy protein with isoflavones, which is consistent with a vasodilatory response, than after treatment with total milk protein. Plasma isoflavones and metabolites were significantly (P < 0.01) higher after treatment with isolated soy protein with isoflavones. There were no significant changes in biochemical cardiovascular disease risk markers or conjugated diene formation between the 3 dietary groups.
Daily consumption of soy protein with isoflavones can result in positive vascular effects that are independent of lipid and antioxidant effects in healthy postmenopausal women.
American Journal of Clinical Nutrition 07/2003; 78(1):123-30. · 6.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to investigate the effects of ovarian hormones on gene expression in the vascular wall. Our approach employed an RT-PCR-based cloning strategy of DNA differential display analysis and verification/confirmation of differential expression by semi-quantitative PCR and real-time PCR. mRNA analysis of normal aortas from intact and ovariectomized female C57BL/6J mice, showed altered expression of 20 genes with significant (>70%) sequence homology to known genes. Eight were selected for further study based on the genes' known function and potential relevance to vascular physiology. Differential expression of mRNA for three genes was confirmed by both semi-quantitative and real-time RT-PCR using gene-specific primers. Ovariectomy downregulated expression of elongation factor-1alpha (3.5-fold), ganglioside-induced differentiation associated protein (8.2-fold), and NADH:ubiquinone oxidoreductase (3.8-fold). Thus, in normal mouse aortas, ovariectomy resulted in significant differential downregulation of a number of vascular genes important to vascular cell growth and angiogenesis, cellular differentiation, and mitochondrial energy metabolism, respectively. These studies have implications for our understanding of hormonal regulation of vascular gene expression and the therapeutic targeting of specific vascular genetic sequences by female sex steroid hormones.
Physiological Genomics 03/2003; 12(3):175-85. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to identify genetic targets in the vasculature for estrogen by profiling genes expressed in female human aortic endothelial cells exposed to various doses of 17 beta-estradiol at differing concentrations and for differing periods of time. Our approach employed a RT-PCR-based cloning strategy of DNA differential display analysis, with differential expression verified by semiquantitative PCR performed with gene-specific primers. A significant increase in mRNA expression in response to 17 beta-estradiol was observed for the following three genes: aldose reductase (3.4-fold), caspase homologue-alpha protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold). For all three upregulated genes, estradiol-induced upregulation occurred with a similar time course and temporally clustered to the first 24 h after hormone treatment. In addition, the effect of estradiol dose on gene expression was consistent and occurred at physiological concentrations. Our results describe previously uncharacterized estradiol-sensitive time- and dose-dependent regulation of genes with potential importance to vascular function in human endothelial cells.
Journal of Applied Physiology 04/2002; 92(3):1064-73. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: HRT may act preventively to reduce morbidity and mortality from cardiovascular disease in primary prevention. The development of SERMs adds a new, exciting, and promising therapeutic option to this field, as does the enhanced availability of soy phytoestrogen products. Although clinical trial data are incomplete, epidemiologic studies suggest that HRT raises HDL-C and triglyceride levels and lowers LDL-C levels. In addition, HRT lowers levels of Lp(a). These changes account for up to 50% of the cardiovascular risk reduction observed with HRT. In contrast, SERMs have less uniform effects. Both SERMs and phytoestrogens are less potent than HRT but have greater tissue selectivity. Although further study is needed, current information suggests that SERMs and phytoestrogens have significant potential to reduce CAD risk and may be a viable alternative to HRT for modest lowering of lipid levels. Phytoestrogens may be particularly useful for reducing CAD risk in men because they do not cause the side effects associated with estrogen. Additional clinical trials are necessary to determine whether the favorable lipid effects associated with HRT, SERMs, and phytoestrogens are linked to protection against cardiovascular disease. Nonetheless, physicians should consider the use of HRT, SERMs, and phytoestrogens for lowering lipid levels and reducing cardiovascular risk in women.
Postgraduate Medicine 02/2002; 111(1):23-30; quiz 3. · 1.78 Impact Factor
