Zinc Ion Inhibits Macrophage Foaming during Atherosclerosis
- VernacularTitle:锌离子抑制动脉粥样硬化进程中的巨噬细胞泡沫化
- Author:
Tian TIAN
1
;
Fang-min ZHOU
1
;
Yong-bo TANG
1
Author Information
1. Zhongshan School of Medicine，Sun Yat-Sen University，Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
atherosclerosis；scavenger receptor；macrophage；zinc；zinc ion transporter
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2019;40(3):321-328
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】To investigate the effects of zinc on the formation of atherosclerotic macrophage foaming and plaque formation and its mechanism.【Methods】The macrophage foaming model was established by stimulating THP-1cells with oxLDL. The degree of foaming in different zinc concentrations of 0，30 and 60 μmol/Lwas detected by oil red Ostaining and the intake of lipid by foam cells was measured by DiI-oxLDL fluorescence. The relevant scavenger protein ex⁃pression of CD36，SR-A was detected by immunoblotting. The relative expression level of zinc ion transporters was detect⁃ed by real-time fluorescent quantitative PCR. ApoE-/- mice were randomly divided into 4 groups，the normal feed group（Chow group），the high-fat zinc-deficient group（HFD-ZnD），and the high-fat normal zinc group（HFD），high-fatand zinc-supplement group（HFD-ZnS），blood lipids and the protein of the mice aorta were detected in the 13 week.【Results】Compared with the normal zinc group，the oil red O density increased（P < 0.05），and add zinc ion decreased
the intake of the DiI-oxLDL by foam cells（P < 0.01）. In the 0 μmol/L zinc group，the SR-A and CD36 protein expressionin the foam cells increased（P < 0.05）and 15μmol/L Zn2+ treatment before stimulating with oxLDL reduced the contentsof SR-A and CD36 proteins（P < 0.05）. Compared the oxLDL-treated group with the control group，the mRNA expres⁃sion levels of ZIP10，ZIP12 and ZIP14 increased，and the mRNA expression levels of ZIP4，ZIP7 and ZIP8 decreased（P < 0.05）；while the mRNA expression of ZnT4 was up-regulated（P < 0.01），and the mRNA expression of ZnT1 was down-regulated（P < 0.05）. Compared with Chow group，low density lipoprotein cholesterol（LDL-C），total cholesterol（TC）and triglyceride（TG）were increased in HFD group and HFD-ZnD group，respectively（P < 0.05）；HFD-ZnD group High-density lipoprotein cholesterol（HDL-C）was significantly elevated. Moreover，the LDL-C of the HFD-ZnS group was significantly lower than that of the HFD-ZnD group（P < 0.05）. The SR-A protein of the mice aorta of the HFD and HFD-ZnD group increased compared to the Chow group（P < 0.01），HFD-ZnS could restrain the increase（P < 0.05）. Compared with the Chow group，the ratio of plaque area in the aorta to the total arterial lumen area was significantly in⁃creased in the HFD-ZnD group（P < 0.01），and HFD-ZnS significantly inhibited this increase（P < 0.01）.【Conclusions】 Extracellular zinc deficiency aggravates lipid deposition in macrophages，and the mechanism may be regulated by up-reg⁃ulating the scavenger receptor CD36 and SR-A. Zinc ion transporters are involved in macrophage foaming and formation ofarterial plaques. Zinc deficiency can increase LDL-C and promote the increase of arterial plaque induced by high-fat diet.
