Fatty acid‐binding Protein‐3 (FABP3) is a Novel Regulator of Endothelial Function

Abstract

Introduction Peripheral Artery Disease (PAD) is characterized by plaque deposition in the arteries that supply blood to the lower extremities. Endothelial dysfunction plays a key role in the development of PAD. Recently, we demonstrated a direct correlation between elevated serum FABP3 (Fatty acid-binding protein-3) and PADs’ severity in patients. However, the role of FABP3 in the endothelium is not known. To understand the pathophysiological role of endothelial FABP3, we hypothesized that FABP3 is a novel regulator of endothelial function. Methods and Results: To test our hypothesis, we cultured human umbilical vein endothelial cells (HUVECs) and confirmed the basal expression of FABP3. HUVECs were then treated with different doses (0, 10, 20, 50 and 80 mg/ml) of oxidized low-density lipoprotein (oxLDL), which is an in vitro model to study atherosclerosis-associated endothelial dysfunction, for 24 hours and the expression level of FABP3 was measured. To our surprise, we observed a significant reduction in the expression level of FABP3 in oxLDL-treated cells in a dose-dependent manner. Next, we measured the expression level of FABP3 in HUVECs using 80 mg/ml of oxLDL and evaluated for FABP3 expression at 0, 6, 12 and 24 hours. We observed a significant reduction in FABP3 expression for 6, 12 and 24 hours of oxLDL treatment with maximum reduction at 24 hours of oxLDL treatment. We also measured the expression level of the fatty acid-binding proteins FABP4 and FABP5 following similar oxLDL treatment to HUVECs and observed a significant down-regulation for both proteins. Next, we transfected HUVECs with siFABP3 or scrambled control to silence FABP3 and confirmed silencing. Loss of FABP3 in HUVECs caused reduced proliferation, which was associated with increased expression of the cell cycle inhibitor protein p21. Conclusion: Our preliminary findings support our hypothesis and warrant investigation. Our data demonstrate that FABP3 is basally expressed in endothelial cells and regulates proliferation. We also, for the first time, report that oxLDL-treatment significantly reduced FABP3 expression in a dose- and time-dependent manner in endothelial cells in vitro. Studies are underway to elucidate the potential role of FABP3 in endothelial cells.