Issue Archive

Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein

NING Yu¹, ZHANG Ming^1,*, DU Yun-Hui², ZHANG Hui-Na², LI Lin-Yi², QIN Yan-Wen², WEN Wan-Wan¹, ZHAO Quan-Ming¹

¹Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China；²Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China

Abstract

It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored. The proliferation, migration and cell aging of macrophages were detected by MTT method, scratch test and β-galactosidase staining respectively. The ELISA method was used to detect the secretion of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1β (IL-1β). Western blot analysis was applied to measure the phosphorylation of focal adhesion kinase (FAK), which was required for the process of proliferation and migration of macrophages. The results showed that oxLDL significantly inhibited the macrophage proliferation and migration, induced cell senescence, and promoted the secretion of TNF-α, MCP-1, and IL-1β; while T4 reversed those effects of oxLDL on macrophage in a concentration-dependent manner. Moreover, oxLDL increased the phosphorylation of FAK in macrophage, while T4 concentration-dependently reversed the effect. These results suggest that T4 modulates macrophage proliferation, migration, senescence, and secretion of inflammation factors in a concentration-dependent way.

Key words: Thyroid hormone; oxidized low-density lipoprotein; Macrophage; hypothyroidism; atherosclerosis

Received: 2017-09-16　　Accepted: 2018-01-30

Corresponding author: 张铭　　E-mail: mzcap@163.com

DOI: 10.13294/j.aps.2018.0015

Citing This Article：

NING Yu, ZHANG Ming, DU Yun-Hui, ZHANG Hui-Na, LI Lin-Yi, QIN Yan-Wen, WEN Wan-Wan, ZHAO Quan-Ming. Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein. Acta Physiol Sin 2018; 70 (2): 141-148 (in Chinese with English abstract).