1,721,134 research outputs found
Selective estrogen receptor isoform agonists improve vascular function and metabolic control: the need to look beyond hormones
No full textAnimal and cellular models for hypolipidemic drugs
No full textBackground: The development of effective and safe lipid-lowering agents should set out from and rely on robust preclinical investigation. Objective: To accomplish this aim, the selection of proper cellular and animal models is crucial. Results: Because lipid-lowering agents are ultimately supposed to reduce the atherosclerotic burden in the arterial wall, they need to tackle directly or indirectly the multifactorial nature of atherosclerotic disease. Hence, these drugs may essentially prevent triglyceride-rich lipoprotein assembly or enhance low-density lipoprotein (LDL) clearance through the LDL or related receptors in the liver. Established animal models such as, the apolipoprotein E- and the LDL-receptor knockout mice are widely used to test drug actions on these pathways. A different approach is testing the ability of candidate drugs to increase plasma high-density lipoprotein (HDL) levels. More recently, the focus has shifted to drugs enhancing HDL function rather than just plasma HDL levels. This in turn requires in vitro and particularly in vivo models of reverse cholesterol transport, which have become available by now. Conclusion: A positive outcome of preclinical studies is necessary but not sufficient for an investigational new drug to be eventually approved for clinical use
Targeting interleukin-1 beta hampers atherosclerosis progression - Is there great promise?
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Emerging role of estrogen in the control of cardiometabolic disease
No full textMenopause is associated with an increased risk of cardiovascular and metabolic disease that is partly independent of aging. This increased risk is largely due to postmenopausal estrogen loss. Estrogen improves insulin sensitivity and ss-cell function. This is consistent with the increased risk of diabetes after menopause and the finding that menopausal hormone therapy (MHT) lowers the incidence of diabetes. Experimental data suggest that estrogen has anti-atherosclerotic and pro-thrombotic properties. This is consistent with observational and interventional studies suggesting that MHT reduces the risk of cardiovascular disease if initiated early in women with a low-risk profile, but might increase risk in older women and/or those with other risk factors (e.g. dyslipidemia). Future research focusing on improving prevention of cardiometabolic disease through MHT may help to identify agents with higher tissue- and estrogen receptor-isoform specificity than currently used hormones
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