Fatty‐acid‐binding protein 4 as a novel contributor to mononuclear cell activation and endothelial cell dysfunction in atherosclerosis

Yen Wen Wu, Ting Ting Chang, Chia Chi Chang, Jaw-Wen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background—Elevated circulating fatty‐acid‐binding protein 4 (FABP4) levels may be linked with cardiovascular events. This study aimed to investigate the mechanistic role of FABP4 in atherosclerosis. Methods—We recruited 22 patients with angiographically proven coronary artery disease (CAD) and 40 control subjects. Mononuclear cells (MNCs) and human coronary endothelial cells (HCAECs) were used for in vitro study. Results—Patients with CAD were predominantly male with an enhanced prevalence of hypertension, diabetes, and smoking history. FABP4 concentrations were up‐regulated in culture supernatants of MNCs from CAD patients, which were positively correlated with the patients’ age, waist–hip ratio, body mass index, serum creatinine, type 2 diabetes, and the presence of hypertension. The adhesiveness of HCAECs to monocytic cells can be activated by FABP4, which was reversed by an FABP4 antibody. FABP4 blockade attenuated the oxidized low‐density lipoprotein (oxLDL)‐induced expression of ICAM‐1, VCAM‐1, and P‐selectin. FABP4 impaired the tube formation and migration via the ERK/JNK/STAT‐1 signaling pathway. FABP4 suppressed phosphorylation of eNOS and expression of SDF‐1 protein, both of which can be reversed by treatment with VEGF. Blockade of FABP4 also improved the oxLDL‐impaired cell function. Conclusion—We discovered a novel pathogenic role of FABP4 in MNC activation and endothelial dysfunction in atherosclerosis. FABP4 may be a therapeutic target for modulating atherosclerosis.

Original languageEnglish
Article number9245
Pages (from-to)1-16
Number of pages16
JournalInternational Journal Of Molecular Sciences
Volume21
Issue number23
DOIs
StatePublished - 1 Dec 2020

Keywords

  • Adhesion molecules
  • Atherosclerosis
  • Coronary artery disease
  • Endothelial dysfunction
  • Fatty acid‐binding protein 4

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