Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although favorable effects of estrogen replacement therapy on atherosclerosis have been recognized, the benefit versus risk of estrogen replacement on overall cardio- vascular health remains controversial. The main adverse effect jeopardizing the clinical usage of estrogen is the increased risk of breast and endometrial cancer. Zearalenone (ZEN) is a universal endogenous hormone possessing estrogen-like effects and facilitating plant growth. alpha-Zearalanol (alpha-ZAL), a new phytoestrogen, is a reductive product of ZEN. Our preliminary evidence suggested that alpha-ZAL is anti-atherosclerotic. The aim of this study was to examine the effect of alpha-ZAL on atherosclerotic formation and serum lipid profile. Adult female nulliparous rabbits were ovariectomized or sham-operated and fed a high-cholesterol diet with different doses of alpha-ZAL or 17beta-estradiol for 12 wk. The aortic intimal atherosclerotic plaque was significantly larger in the cholesterol-fed group compared to control and sham groups. alpha-ZAL and 17beta-estradiol treatments significantly reduced plaque formation and improved serum profile of lipid (TC, TG, HDL-C, and LDL-C) and lipoprotein (ApoAl and ApoB). Both alpha-ZAL and 17beta-estradiol reconciled ovariectomy-induced uterine atrophy, although alpha-ZAL was significantly less potent than 17beta-estradiol in stimulating uterine growth. Our findings indicate that the phytoestrogen alpha-ZAL has an important anti-atherogenic property, analogous to that of estrogen.
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PMID:Phytoestrogen alpha-zearalanol inhibits atherogenesis and improves lipid profile in ovariectomized cholesterol-fed rabbits. 1571 Oct 25

alpha-Zearalanol (alpha-ZAL), a phytochemical with both antioxidant and estrogen-like properties, has been shown to retard progression of atherosclerosis and regulate cardiovascular function in part through suppression of endothelin-1 (ET-1) secretion. However, the precise nature behind alpha-ZAL-elicited inhibition on ET-1 cascade is not largely known. Oxidized low density lipoprotein (oxLDL) plays a critical role in the expression and secretion of ET-1 as well as the onset and progression of atherosclerosis through accumulation of reactive oxygen species (ROS) and activation of mitogen-activated protein kinase stress signaling cascade. Therefore, this study was designed to examine the effect of alpha-ZAL on oxLDL-induced extracellular signal-regulated kinase (ERK) phosphorylation, ROS generation, activation of the transcriptional factor activator protein-1 (AP-1), expression, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVEC). ROS generation was monitored using 2,7-dichlorofluorescin fluorescence. ET-1 expression and promoter activity were evaluated by RT-PCR and luciferase assays, respectively. oxLDL (35 microg/ml) significantly enhanced ERK phosphorylation, ROS generation, AP-1 activity, mRNA expression, secretion and promoter activity of ET-1 in HUVECs, all of which were abrogated by alpha-ZAL and the antioxidant N-acetyl-l-cysteine. Collectively, these data favor the notion that alpha-ZAL antagonizes oxLDL-induced upregulation of ET-1 gene expression and secretion via suppression of oxLDL-induced ROS accumulation, ERK phosphorylation, and activation of the endothelial transcriptional factor AP-1.
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PMID:alpha-Zearalanol attenuates oxLDL-induced ET-1 gene expression, ET-1 secretion and redox-sensitive intracellular signaling activation in human umbilical vein endothelial cells. 1857 20