Journal ArticleDOI
Raloxifene, tamoxifen and vascular tone.
Fung Ping Leung,Suk Ying Tsang,Chi-Ming Wong,Lai Ming Yung,Yau Chi Chan,Hok Sum Leung,Xiaoqiang Yao,Yu Huang +7 more
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TLDR
The outcome of the Raloxifene Use for the Heart (RUTH) trial will determine whether ralox ifene, currently approved for the treatment of post‐menopausal osteoporosis, could substitute for HRT in alleviating cardiovascular symptoms in post-menopausal women.Abstract:
1. Oestrogen deficiency causes progressive reduction in endothelial function. Despite the benefits of hormone-replacement therapy (HRT) evident in earlier epidemiological studies, recent randomized trials of HRT for the prevention of heart disease found no overall benefit. Instead, HRT users had higher incidences of stroke and heart attack. Most women discontinue HRT because of its many side-effects and/or the increased risk of breast and uterine cancer. This has contributed to the development of selective oestrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, as alternative oestrogenic agents. 2. A SERM is a molecule that binds with high affinity to oestrogen receptors but has tissue-specific effects distinct from oestrogen, acting as an oestrogen agonist in some tissues and as an antagonist in others. Clinical and animal studies suggest multiple cardiovascular effects of SERMs. For example, raloxifene lowers serum levels of cholesterol and homocysteine, attenuates oxidation of low-density lipoprotein, inhibits endothelial-leucocyte interaction, improves endothelial function and reduces vascular smooth muscle tone. 3. Available evidence suggests that raloxifene and tamoxifen are capable of acting directly on both endothelial cells and the underlying vascular smooth muscle cells and cause a multitude of favourable modifications of the vascular wall, which jointly contribute to improved local blood flow. The outcome of the Raloxifene Use for the Heart (RUTH) trial will determine whether raloxifene, currently approved for the treatment of post-menopausal osteoporosis, could substitute for HRT in alleviating cardiovascular symptoms in post-menopausal women.read more
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Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophages
Allison B. Reiss,Steven E. Carsons,Kamran Anwar,Soumya Rao,Sari D Edelman,Hongwei Zhang,Patricia Fernandez,Bruce N. Cronstein,Edwin S. L. Chan +8 more
TL;DR: This study provides evidence supporting the notion of an atheroprotective effect of methotrexate, and reports the first reported evidence that any commonly used medication can increase expression of antiatherogenic reverse cholesterol transport proteins and can counteract the effects of COX-2 inhibition.
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Molecular therapy of breast cancer: progress and future directions.
TL;DR: The systematic study of estrogen activation pathways suggests that the enzymes steroid sulfatase and 17β-hydroxysteroid dehydrogenase type 1, which both have pivotal roles in estrogen biosynthesis, are promising targets; the results of a phase I trial of steroid sulf atase inhibitors are encouraging.
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Endothelial Dysfunction: The Common Consequence in Diabetes and Hypertension
TL;DR: Specific therapies targeting reactive oxygen species using antioxidants and inhibitors of the rennin-angiotensin system or increasing endothelial nitric oxide synthase activity might assist to reverse endothelial dysfunction and thus reduce the related cardiovascular morbidity and mortality in diabetes and hypertension.
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Gender Differences in Ocular Blood Flow
TL;DR: Gender differences in the epidemiology of the most frequent ocular diseases that have been found to be associated with impaired ocular blood flow, such as age-related macular degeneration, glaucoma and diabetic retinopathy are reviewed.
Journal ArticleDOI
Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats.
A.Z. Lamas,Izabela Facco Caliman,Polyana Lima Meireles Dalpiaz,Antonio Ferreira de Melo,Gláucia R. Abreu,Elenice Moreira Lemos,Sonia Alves Gouvea,Nazaré Souza Bissoli +7 more
TL;DR: The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period.
References
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Journal ArticleDOI
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial
Jacques E. Rossouw,Garnet L. Anderson,Ross L. Prentice,Andrea Z. LaCroix,Charles Kooperberg,Marcia L. Stefanick,Rebecca D. Jackson,Shirley A.A. Beresford,Barbara V. Howard,Karen C. Johnson,Jane Morley Kotchen,Judith K. Ockene +11 more
TL;DR: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Journal ArticleDOI
Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.
Pierre D. Delmas,Nina H. Bjarnason,Bruce H. Mitlak,Anne-Catherine Ravoux,Aarti Shah,William J. Huster,Draper Michael William,Claus Christiansen +7 more
TL;DR: Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.
Journal ArticleDOI
Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial
Trevor J. Powles,Ros Eeles,Sue Ashley,Doug Easton,Jenny C. Chang,Mitch Dowsett,A. Tidy,Jenny Viggers,Jane B. Davey +8 more
TL;DR: The authors have been unable to show any effect of tamoxifen on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction inhealthy women given tamoxIFen versus placebo.
Journal ArticleDOI
Vasoregulation by the β1 subunit of the calcium-activated potassium channel
Robert Brenner,Guillermo J. Pérez,Adrian D. Bonev,Delrae M. Eckman,Jon C. Kosek,Steven W. Wiler,Andrew J. Patterson,Mark T. Nelson,Richard W. Aldrich +8 more
TL;DR: It is shown that targeted deletion of the gene for the β1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure.
Journal ArticleDOI
Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women
Brian W. Walsh,Lewis H. Kuller,Robert A. Wild,Sofia Paul,Mildred Farmer,Jeffry B. Lawrence,Aarti S. Shah,Pamela W. Anderson +7 more
TL;DR: Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides.