Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective estrogen receptor modulators (SERMs) have offered the promise of reducing the burden of coronary artery disease (CAD) in postmenopausal women, based on the positive effects recorded on intermediate markers (blood lipids and markers of inflammation). The effects of raloxifene, bazedoxifene and lasofoxifene on cardiovascular endpoint markers are presented as reported in recent, randomized, controlled trials. Raloxifene failed to significantly lower the risk of CAD in postmenopausal osteoporotic women, without any effect on stroke or early harm, but doubling the risk of venous thromboembolism. The risk of CAD was lowered in a subgroup of patients at risk of CAD. In a large randomized, controlled trial with CAD as the primary endpoint in patients at risk of CAD, raloxifene failed to significantly reduce CAD, while significantly increasing the incidence of fatal stroke and venous thromboembolism. Bazedoxifene, in an osteoporosis trial, had similar effects on the cardiovascular system when compared to raloxifene. Lasofoxifene has only been studied in postmenopausal osteoporotic women in the PEARL trial. Lasofoxifene reduced the risk of coronary heart disease events as well as the risk of stroke, while the risk of deep vein thrombosis remained in line with other SERMs. These results will need to be confirmed in a study with primary cardiovascular endpoints. Until then, it is unlikely that SERMs will play a major role in strategies aimed at the prevention of coronary heart disease in postmenopausal women.
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PMID:Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. 1981 Dec 53

Pregnant women show a low level of protein S (PS) in plasma, which is known to be a risk for deep venous thrombosis. 17Beta-estradiol (E(2)), an estrogen that increases in concentration in the late stages of pregnancy, regulates the expression of various genes via the estrogen receptor (ER). Here, we investigated the molecular mechanisms behind the reduction in PS levels caused by E(2) in HepG2-ERalpha cells, which stably express ERalpha, and also the genomic ER signaling pathway, which modulates the ligand-dependent repression of the PSalpha gene (PROS1). We observed that E(2) repressed the production of mRNA and antigen of PS. A luciferase reporter assay revealed that E(2) down-regulated PROS1 promoter activity and that this E(2)-dependent repression disappeared upon the deletion or mutation of two adjacent GC-rich motifs in the promoter. An electrophoretic mobility shift assay and DNA pulldown assay revealed that the GC-rich motifs were associated with Sp1, Sp3, and ERalpha. In a chromatin immunoprecipitation assay, we found ERalpha-Sp protein-promoter interaction involved in the E(2)-dependent repression of PROS1 transcription. Furthermore, we demonstrated that E(2) treatment recruited RIP140 and the NCoR-SMRT-HDAC3 complex to the PROS1 promoter, which hypoacetylated chromatin. Taken together, this suggested that E(2) might repress PROS1 transcription depending upon ERalpha-Sp1 recruiting transcriptional repressors in HepG2-ERalpha cells and, consequently, that high levels of E(2) leading to reduced levels of plasma PS would be a risk for deep venous thrombosis in pregnant women.
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PMID:Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex. 2020 Jan 60

Current guidelines recommend that hormone therapy (HT) in postmenopausal women with a uterus include a progestin to protect against endometrial hyperplasia. However, many concerns relating to HT use appear to be related to the progestin component, including cardiovascular risk, breast stimulation, and irregular vaginal bleeding. Conjugated estrogens (CE) combined with the selective estrogen receptor modulator bazedoxifene (BZA) is a new progestin-free HT option for alleviating estrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestin-containing therapy is not appropriate. Five double-blind, randomized, placebo-controlled, phase 3 studies, known as the Selective estrogens, Menopause, And Response to Therapy (SMART) trials have investigated the efficacy of CE/BZA for relieving vasomotor symptoms (VMS), and effect on bone mass, as well as endometrial and breast safety in postmenopausal women. In a 12-week study, CE 0.45 mg/BZA 20 mg significantly reduced the number and severity of hot flushes compared with placebo at weeks 4 and 12. Unlike estrogen-progestin therapy (EPT), CE 0.45 mg/BZA 20 mg did not increase breast density compared with placebo. In clinical trials up to 2 years, CE/BZA had a favorable tolerability profile, demonstrated by amenorrhea rates similar to placebo. Vascular disorders including venous thromboembolic events (pulmonary embolism, retinal vein thrombosis, deep vein thrombosis, and thrombophlebitis) were rare events, occurring in less than 1 per 1000 patients. CE/BZA was associated with significantly higher incidences of amenorrhea and lower incidences of bleeding compared with CE/medroxyprogesterone acetate in 2 comparative trials. Therefore, CE 0.45 mg/BZA 20mg provides an effective, well-tolerated, progestin-free alternative to EPT for postmenopausal women with a uterus.
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PMID:Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deficiency symptoms of menopause: a practical guide. 2568 82


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