GDF-15 Suppresses Atherosclerosis by Inhibiting oxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

Hong Huang; Zhongli Chen; Yan Li; Kunmei Gong; Le Xiao; Hao Fu; Jingjing Yang; Xianying Wang; Qiang Meng

doi:10.1155/2021/6497568

GDF-15 Suppresses Atherosclerosis by Inhibiting oxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

Evid Based Complement Alternat Med. 2021 Sep 7:2021:6497568. doi: 10.1155/2021/6497568. eCollection 2021.

Authors

Hong Huang^{1

2}, Zhongli Chen³, Yan Li², Kunmei Gong⁴, Le Xiao⁴, Hao Fu⁵, Jingjing Yang², Xianying Wang², Qiang Meng⁵

Affiliations

¹ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
² Department of Geriatric Medicine, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming 650032, China.
³ Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, China.
⁴ Department of General Surgery, The First People's Hospital of Yunnan Province, Kunming 650032, China.
⁵ Department of Neurology, The First People's Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China.

Abstract

The growth differentiation factor-15 (GDF-15) may be involved in atherosclerosis. However, the role of GDF-15 in atherosclerosis remains unclear. The main goal of this study was to verify the role and mechanism of GDF-15 in atherogenesis. We first compared the serum GDF-15 level between patients with coronary atherosclerosis and healthy people. And then one ApoE^-/- mouse model of atherosclerosis was used to explore the effects of GDF-15 on oxidized low-density lipoprotein (oxLDL) accumulation, atherosclerosis-related gene expression, and lipid accumulation-related protein expression in mouse macrophages. As a result, the level of serum GDF-15 in patients with coronary atherosclerosis was significantly higher than that in healthy people. In the mouse model, GDF-15 expression was elevated in the core of plaque, and it was secreted mainly by the macrophages. In addition, GDF-15 decreased oxLDL-induced lipid accumulation and inflammation activation in macrophages. GDF-15 decreased the mRNA expressions of CD36, LOX1, and TLR4 that are associated with lipoprotein accumulation in macrophages. Further study showed that GDF-15 might suppress oxLDL-induced lipoprotein accumulation via inhibiting CD36 and LOX1 and decrease inflammation in macrophages by inhibiting TLR4. Thus, GDF-15 may suppress atherosclerosis and plaque formation by inhibiting lipoprotein accumulation and inflammation activation.