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 (TR alpha 1) and MAPK pathway. TR alpha 1 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 TR alpha 1-Erk1/2 pathway and inhibiting oxidative stress, which implies a potential mechanism of hypothyroid-accelerated atherosclerosis.

Automated summary

Increasing evidence suggests that hypothyroidism exacerbates atherosclerosis. Macrophage apoptosis is crucial in atherosclerotic plaque development. The study reveals that thyroid hormones attenuate oxLDL-induced macrophage apoptosis by activating the TR alpha 1-Erk1/2 pathway and inhibiting oxidative stress in a concentration-dependent manner, indicating a potential mechanism for hypothyroidism-accelerated atherosclerosis.