Abstract 15338: The Essential Role of Fatty-Acid Binding Protein 3 in Endothelial Function

Abstract

Background: The endothelium lines blood vessel’s inner walls and interacts directly with the circulation, systemically influencing whole-body physiology through endothelial function. Fatty acid binding protein 3 (FABP3), abundant in myocardiocytes, serve as effective cardiac injury’s biomarkers when presented in circulation. Our lab has preliminary found that endothelial cells (ECs) express FABP3. The role of FABP3 in endothelial function and FABP3 exposure’s effects on ECs are unknown. Objective: Evaluate FABP3’s role in endothelial dysfunction. Method: Human umbilical vein endothelial cells (HUVECs) were grown under cell culture standards (370 C, 5% CO2) prior to treatment by lipopolysaccharide (LPS). FABP3 expression in treated HUVECs was evaluated by qPCR. Next, FABP3-silencing RNAs were transfected into HUVECs to knock-down FABP3 for 24 hours. HUVECs were also exposed to recombinant FABP3 as a gain of function model. HUVECs were then treated with LPS for 24 hours before subjected to molecular/phenotypic evaluation for aspects of endothelial function (migration, proliferation, angiogenesis, inflammation). The Delta-Ct method and One-way ANOVA with Tukey (HSD) test were used to analyze data from qPCR and comparisons between treatment groups, respectively; p-value < 0.05 is considered significant. Results: 1) FABP3 is basally expressed in ECs, 2) LPS upregulated endothelial FABP3 expression; 3) loss of FABP3 protected ECs against LPS-induced endothelial dysfunction; FABP3 exposure exacerbated LPS-induced inflammation; 4) loss of FABP3 protects ECs against LPS-induced stress by promoting cell survival, anti-inflammatory and pro-angiogenic pathways. Conclusions: We identified the novel and basal expression of FABP3 in ECs and demonstrated that FABP3 influences endothelial function at both the molecular and phenotypic levels under stress in vitro. Loss- and gain- of endothelial FABP3 ameliorates and exacerbates LPS-induced endothelial dysfunction, respectively, by affecting cell survival and inflammatory and angiogenic pathways. Our findings suggest that circulating FABP3 may be detrimental to the endothelium; therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in myocardial injury.