The Effect of Fatty Acid-Binding Protein 3 Exposure on Endothelial Transcriptomics

Background: Fatty acid-binding protein 3 (FABP3) is released in circulation following myocardial infarction, and an increased level of circulatory FABP3 has also been reported in peripheral artery disease patients, exposing endothelial cells to higher levels of FABP3. Recently, loss of endothelial FABP3 was shown to protect endothelial cells against inflammation-induced endothelial dysfunction; however, the effect of FABP3 exposure on endothelial cells is unknown. Accordingly, to study the effect of FABP3 exposure on endothelial cells, we performed transcriptomic profiling following recombinant human FABP3 (rhFABP3) treatment of endothelial cells. Methods: Cultured human endothelial cells were treated with either a vehicle or rhFABP3 (50 ng/mL, 6 h); then, RNA sequencing was performed. Gene expression analysis followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was performed to identify differentially expressed genes and affected cellular functions and pathways. Results: Differential gene expression analysis revealed kinesin family member 26b (KIF26B) to be the most upregulated and survival of motor neuron 2 (SMN2) to be the most downregulated genes in rhFABP3-treated compared to vehicle-treated endothelial cells. Most of the differentially expressed genes were associated with endothelial cell motility, immune response, and angiogenesis. GO and KEGG analyses indicated that rhFABP3 exposure impacts several crucial pathways, predominantly “Regulation of leukocyte mediated cytotoxicity” and “Natural killer cell mediated cytotoxicity”, suggesting its involvement in endothelial cell physiology and response mechanisms to cardiovascular stress. Conclusions: This is the first study to evaluate rhFABP3-induced transcriptomics in human endothelial cells. Our data reveal novel genes and pathways affected by the exposure of endothelial cells to FABP3. Further research is necessary to validate these findings and fully understand FABP3’s role in endothelial biology and in cardiovascular diseases like myocardial infarction and peripheral artery disease.