Fatty-Acid-Binding Protein 4 as a Novel Contributor to Mononuclear Cell Activation and Endothelial Cell Dysfunction in Atherosclerosis.

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.

• Authors: Yen-Wen Wu, Ting-Ting Chang, Chia-Chi Chang, Jaw-Wen Chen
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 23 (Dec 03 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33287461 (Publication Type: Journal Article)

Chemical References

• CD18 Antigens
• Cell Adhesion Molecules
• FABP4 protein, human
• Fatty Acid-Binding Proteins
• Integrin alpha Chains
• Lipoproteins, LDL
• STAT1 Transcription Factor
• oxidized low density lipoprotein
• NOS3 protein, human
• Nitric Oxide Synthase Type III
• Extracellular Signal-Regulated MAP Kinases

Topics

• Aged
• Atherosclerosis (etiology, metabolism, pathology)
• CD18 Antigens (metabolism)
• Cell Adhesion
• Cell Adhesion Molecules (genetics, metabolism)
• Disease Susceptibility
• Endothelial Cells (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fatty Acid-Binding Proteins (metabolism)
• Female
• Humans
• Integrin alpha Chains (metabolism)
• Leukocytes, Mononuclear (immunology, metabolism)
• Lipoproteins, LDL (metabolism)
• Male
• Middle Aged
• Models, Biological
• Nitric Oxide Synthase Type III (genetics, metabolism)
• STAT1 Transcription Factor (metabolism)
• Signal Transduction