Effects of intermittent hypoxia and/or TNF-alpha on E- and A-FABP expression by human aortic endothelial cells in vitro

Abstract

RATIONALE: Fatty acid-binding proteins (FABPs) are members of the lipid-binding proteins (LBPs) superfamily, regulating the fatty acid uptake and intercellular transport. Among 9 subtypes identified with tissue-specific distribution, E- and A-FABP have been found to mediate atherosclerosis in animals. Obstructive sleep apnea (OSA) characterized by recurrent intermittent hypoxia (IH), is closely associated with atherosclerosis. On the other hand, TNF-α is a prominent pro-inflammatory cytokine that induces monocyte migration into endothelial cells, thus initiating or accelerating atherosclerosis. This study was to explore the effects of IH and/or TNF-α on E- and A-FABP expression by endothelial cells in vitro. METHODS: Human abdominal aortic endothelial cells (HAAE) were exposed to intermittent normoxia (IN as control) or IH [a 5-min hypoxia (5% O2) followed by a 10-min normoxia (21% O2) for 64 cycles using the BioSpherix OxyCycler C42 system] in the absence or presence of TNF-α. The mRNA levels of E- and A-FABP in HAAE were determined using RT-PCR. RESULTS: IH alone significantly upregulated E- and A-FABP mRNA (1.25-fold and 1.44-fold vs control for E- and A-FABP respectively, p < 0.05; n =4). The combination of TNF-α with IH caused additive effect on elevated mRNA expressions of E- and A-FABP (1.81-fold and 2.4-fold vs control for E- and A-FABP respectively, p < 0.05; n =4). CONCLUSION: We found that IH alone led to upregulation, and to further enhancement of E- and A-FABP expression in presence of TNF-α by endothelial cells. Since elevated circulating TNF-α level has been described in OSA, our data suggests that OSA may be prone to upregulation of E- and A-FABP expression and thus atherosclerosis due to IH and inflammation.