Oxidized Low-Density Lipoproteins Impair Endothelial Function by Inhibiting Non-Genomic Action of Thyroid Hormone–Mediated Nitric Oxide Production in Human Endothelial Cells

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 W...