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• W2088862034 abstract "Background: Thyroid hormone (TH) plays an important role in the modulation of cardiac function, including contractility and systemic vascular resistance (SVR). 3,5,3′-triiodothyronine (T3), the active form of TH, induces the activation of endothelial nitric oxide synthase via PI3K/AKT non-genomic signaling. Hypothyroidism is associated with an increase in SVR and serum low-density lipoproteins (LDL) levels, and accumulation of oxidized LDL (oxLDL) may impair endothelial-dependent vascular relaxation. The aim of this study was to investigate the effects of both native LDL (nLDL) and oxLDL on T3-mediated AKT phosphorylation, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) production in human endothelial cells. Methods: Human umbilical vein endothelial cells were exposed to either nLDL or oxLDL for 3 hours and then stimulated with T3 (10−7 M) or pretreated with an antioxidant mixture of vitamins E and C for 12 hours before treatment with LDL. An analysis of AKT phosphorylation was performed by Western blot, and NO production was evaluated by using 4,5-diaminofluorescein diacetate. Intracellular production of cGMP was measured by enzymatic immunoassay. LDL oxidation was carried out by incubating LDL with CuSO4, and α-tocopherol content of LDL was evaluated by high-performance liquid chromatography. Results: OxLDL impaired T3-mediated AKT phosphorylation at serine 473 and significantly decreased the production of both NO (oxLDL+T3 vs. T3, 9.79±0.5 AU vs. 80.75±2.8 AU, mean±standard deviation, p<0.0001) and cGMP. Furthermore, pretreatment with the antioxidant mixture obviated the inhibitory effect of LDL on T3 action. Conclusions: The results of this study demonstrate that oxLDL may contribute to a blunting of the non-genomic action of T3 and impair the effect of T3 on NO and cGMP production in endothelial cells. These data suggest that oxLDL, apart from inducing the atherosclerotic process, may also promote a mechanism of peripheral resistance to T3, further amplifying the impact of hypothyroidism on endothelial function by increasing SVR." @default.
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• W2088862034 date "2013-02-01" @default.
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• W2088862034 title "Oxidized Low-Density Lipoproteins Impair Endothelial Function by Inhibiting Non-Genomic Action of Thyroid Hormone–Mediated Nitric Oxide Production in Human Endothelial Cells" @default.
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• W2088862034 doi "https://doi.org/10.1089/thy.2011.0524" @default.
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