Foam Cell-Derived CXCL14 Muti-Functionally Promotes Atherogenesis and Is a Potent Therapeutic Target in Atherosclerosis

  • J Cardiovasc Transl Res. 2020 Apr;13(2):215-224. doi: 10.1007/s12265-019-09915-z.
Weilin Tong  1  2 ,  Yaqi Duan  1  2 ,  Rumeng Yang  1  2 ,  Ying Wang  1  2 ,  Changqing Peng  1  2 ,  Zitian Huo  3  4 ,  Guoping Wang  5  6
Affiliations
  • 1. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China.
  • 2. Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China.
  • 3. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China. [email protected].
  • 4. Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China. [email protected].
  • 5. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China. [email protected].
  • 6. Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China. [email protected].
PMID: 31728901 DOI: 10.1007/s12265-019-09915-z
Abstract

CXC chemokine family has been related to atherogenesis for long. However, the relationship between CXCL14 and atherogenesis is still unclear. This study preliminarily detected CXCL14 expression at foam cells in atherosclerosis specimens by immunohistochemistry. In vitro foam cells were derived from THP-1 after phorbol-12-myristate-13-acetate (PMA) and oxidized low-density lipoprotein (ox-LDL) stimulation. Immunoblotting and qPCR convinced CXCL14 expression variation during foam cell formation. We further demonstrated that ox-LDL regulated CXCL14 expression by AP-1. AP-1 could bind to CXCL14 promoter and up-regulate CXCL14 mRNA expression. Besides, CXCL14 promoted THP-1 migration, macrophage lipid phagocytosis, and smooth muscle cell migration as well as proliferation mainly via the ERK1/2 pathway. Additionally, a CXCL14 peptide-induced immune therapy showed efficacy in apoE-/- mouse model. In conclusion, our study demonstrated that CXCL14 is highly up-regulated during foam cell formation and promotes atherogenesis in various ways. CXCL14 may be a potent therapeutic target for atherosclerosis.

Keywords
Atherogenesis; CXCL14; Foam cell.
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