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

Abstract

Introduction: Fatty acid-binding proteins (FABPs) are members of the lipid-binding proteins (LBPs) superfamily, regulating the fatty acid uptake and intercellular transport. Among nine subtypes identified with tissue-specific distribution, E- and A-FABP have been found to mediate atherosclerosis in animals. Obstructive sleep apnoea (OSA), characterised by recurrent intermittent hypoxia (IH) during nocturnal sleep, is closely associated with atherosclerosis. Circulating levels of proinflammatory cytokine TNF-alpha are increased in OSA. The objective of our study was to explore the effects of IH and/or TNF-alpha on E- and A-FABP expression by endothelial cells in vitro. Methods: Human abdominal aortic endothelial cells (HAAEC) 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 [BioSpherix, Redfield, NY]), in the absence or presence of TNF-alpha. The mRNA levels of E- and A-FABP in HAAEC were determined using RT-PCR. Results: IH alone significantly up-regulated 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 IH and TNF-alpha 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 up-regulation, and to further enhancement of E- and A-FABP expression in presence of TNF-alpha by endothelial cells. Since elevated circulating TNF-alpha levels have been described in OSA, our data suggest that OSA may be prone to up-regulation of E- and A-FABP expression and thus atherosclerosis due to IH and inflammation. Acknowledgement: This study was supported by HKU-CRCG Seeding Funding for Basic Research.