Thyroid hormones inhibit apoptosis of macrophage induced by oxidized low-density lipoprotein

Increasing evidence suggests that hypothyroidism aggravates atherosclerosis. Macrophage Apoptosis plays a significant role in the development of atherosclerotic plaque. We aimed to explore the effect of thyroid Hormones on macrophage Apoptosis induced by oxidized low-density lipoprotein (oxLDL). Peripheral blood samples from 20 patients (normal group, hypothyroidism group, coronary artery disease [CAD] group, hypothyroidism + CAD group) were collected to perform messenger RNA microarray analysis. Bioinformatics analysis identified Apoptosis and mitogen-activated protein kinase (MAPK) signaling as differentially expressed pathways between CAD and hypothyroidism + CAD group. In vitro, thyroid Hormones concentration-dependently promoted cell survival and inhibited Apoptosis in oxLDL-treated RAW264.7 macrophages, along with elevated extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation. The STRING database showed an interaction of Thyroid Hormone Receptor alpha1 (TRα1) and MAPK pathway. TRα1 knockdown increased cell Apoptosis and decreased ERK1/2 phosphorylation. ERK1/2 inhibitor aggravated macrophage Apoptosis. Moreover, thyroid Hormones inhibited oxidative stress in oxLDL-treated macrophages. The study indicates that thyroid Hormones concentration-dependently attenuate oxLDL-induced macrophage Apoptosis through activating TRα1-Erk1/2 pathway and inhibiting oxidative stress, which implies a potential mechanism of hypothyroid-accelerated atherosclerosis.