Fatty acid binding protein 3 activates endothelial adhesion of circulating monocytes and impairs endothelial angiogenesis

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BACKGROUND AND PURPOSE: Vascular inflammation and endothelial dysfunction cause the development of atherosclerotic cardiovascular diseases including coronary artery disease (CAD). While elevated fatty acid binding protein 3 (FABP3) may be associated with the presence of cardiovascular diseases, its mechanistic effects remain unclear. This study aimed to investigate the role of FABP3 in impaired angiogenesis and the development of atherosclerosis in CAD. EXPERIMENTAL APPROACH: In total, 1104 patients were enrolled in a clinical observational study and the correlation between serum FABP3 and cardiovascular events were analysed. Another group of CAD patients and non-CAD subjects were enrolled, and their plasma FABP3 concentrations were measured. Primary cultured mononuclear cells endothelial progenitor cells and human coronary artery endothelial cells were used in vitro. Matrigel plug neovascularisation assay and the aortic ring assay were used in wild-type and apolipoprotein E-knockout mice in vivo. KEY RESULTS: Circulating FABP3 was up-regulated in the cardiovascular event-positive group and in the CAD patients. Mononuclear cells from the CAD patients presented increased expression of FABP3. FABP3 enhanced the expression of adhesion molecules, including integrin β2, integrin α4 and PSGL1 in mononuclear cells. FABP3 caused endothelial cell dysfunction through the ERK/p38/STAT1/VEGF signalling pathway. Moreover, oxLDL or TNF-α stimulations impaired endothelial cell function through FABP3-dependent signalling pathways. FABP3 also impaired in vivo angiogenesis. CONCLUSION AND IMPLICATIONS: This study elucidates the clinical and pathological impact of FABP3 on atherosclerotic CAD. Future research may be necessary to evaluate whether FABP3 could be a therapeutic target, especially with regard to stable CAD.

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