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Impact of bazedoxifene on endothelial health markers

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Impact of bazedoxifene on endothelial health markers

dc.contributor.advisor	Cano Sánchez, Antonio
dc.contributor.advisor	Gómez Gallego, Raúl
dc.contributor.advisor	Tarín, Juan José
dc.contributor.author	Dudenko Lozenko, Darya
dc.contributor.other	Facultat de Medicina i Odontologia	es_ES
dc.date.accessioned	2020-06-22T07:48:25Z
dc.date.available	2020-06-23T04:45:05Z
dc.date.issued	2020	es_ES
dc.date.submitted	30-06-2020	es_ES
dc.identifier.uri	https://hdl.handle.net/10550/75152
dc.description.abstract	Atherosclerosis and its most significant clinical repercussion, cardiovascular disease (CVD), is the leading cause of morbidity and mortality in postmenopausal women, with a substantial global public health impact as a consequence. Vascular endothelial dysfunction, which is potentiated by decreasing estrogen levels in the menopausal transition period, is an early hallmark of developing CVD. The action of estrogens has been widely investigated in many critical areas of atherogenesis, due to the presence of estrogen receptors in the vascular system. Estrogens can have both positive and negative effects on the vascular wall depending on the stage of atherosclerosis disease. The estrogen response is mediated by different mechanisms, involving either genomic pathways requiring ligand-activated transcription with posterior modulation of protein synthesis, or non-genomic pathways, mainly affecting enzyme activity and rapid signaling cascades. The vigorous debate surrounding the risk/benefit profile of estrogen in the development and timing of CVD in postmenopausal women is still ongoing. Evidence that the progestin component of hormone therapy increases breast cancer risk or even attenuates the potential beneficial effects of estrogens has been paralleled by a decline in the use of hormone therapy in postmenopausal women in recent years. This data, along with problems associated with long-term use of bisphosphonates, has shifted the focus of recent research to other molecules capable of activating estrogen receptors, leading to transcriptional activity in some tissues but not in others. Selective estrogen receptor modulators (SERMs) and more recently, tissue selective estrogen complex (TSEC) have been developed as alternatives to hormonal replacement therapy (HRT).Previous experimental studies have shown the capacity of estrogens and second-generation SERM raloxifene to promote endothelial cell regrowth and improve cell survival rate in the early stages of atherosclerosis disease. Clinical trials involving bazedoxifene or conjugated estrogens plus bazedoxifene have shown cardiovascular safety in healthy postmenopausal women. However, one research group working with an atherosclerotic animal model in monkeys demonstrated that therapeutic application of bazedoxifene had no effect on atherosclerosis. What is more, bazedoxifene completely impeded the antiatherosclerotic effects of estrogen treatment in the mentioned study. To date no report has been published of bazedoxifene’s effect on vascular cell proliferation and the mechanisms involved using an in vitro model.Previous experimental studies have shown the capacity of estrogens and second-generation SERM raloxifene to promote endothelial cell regrowth and improve cell survival rate in the early stages of atherosclerosis disease. Clinical trials involving bazedoxifene or conjugated estrogens plus bazedoxifene have shown cardiovascular safety in healthy postmenopausal women. However, one research group working with an atherosclerotic animal model in monkeys demonstrated that therapeutic application of bazedoxifene had no effect on atherosclerosis. What is more, bazedoxifene completely impeded the antiatherosclerotic effects of estrogen treatment in the mentioned study. To date no report has been published of bazedoxifene’s effect on vascular cell proliferation and the mechanisms involved using an in vitro model.	es_ES
dc.format.extent	193 p.	es_ES
dc.language.iso	en	es_ES
dc.subject	bazedoxifene	es_ES
dc.subject	estradiol	es_ES
dc.subject	endothelium	es_ES
dc.subject	menopause	es_ES
dc.subject	proliferation	es_ES
dc.title	Impact of bazedoxifene on endothelial health markers	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS	es_ES
dc.embargo.terms	0 days	es_ES