Differential effects of intermittent hypoxia and/or cigarette smoking on the expression levels of fatty acid-binding protein in rat heart and lung: an in vivo pilot study

Abstract

BACKGROUND/PURPOSE: The fatty acid-binding protein (FABP) family comprises of nine subtypes with organ-specific expression, some of which are associated with organ injury. Intermittent hypoxia (IH), a prominent feature of obstructive sleep apnoea (OSA), may lead to ischemia/repurfusion-related tissue injury, while cigarette smoking (CS), the main cause of chronic obstructive pulmonary disease (COPD), is known to cause lung parenchymal destruction. To establish a rat model in the investigation whether IH and/or CS exposure would induce changes of FABP mRNA expressions in heart and lung tissues. METHODS: Male Sprague-Dawley rats were randomly divided into four groups: sham air (SA) or cigarette smoking (CS) plus intermittent normoxia (IN) or intermittent hypoxia (IH). The SA or CS exposure was performed in the ventilated smoking chamber for 1 h, followed by IN or IH exposure using OxyCycler A84 System (BioSpherix, Redfield, NY, USA) daily. The IH profile was characterized by 1.5-min hypoxia (10% oxygen) followed by 4.5-min normoxia (21% oxygen) for 6 h. Rats were sacrificed after 14 days and FABPs (H-, A-, and E-FABP) mRNA levels in heart and lung tissues were determined by RT-PCR. RESULTS: All three FABP subtypes were expressed in both heart and lung tissues, with higher expression levels detected in the heart. Neither H- nor A-FABP expression was found to be affected by IH or CS in both tissues, while E-FABP significantly upregulated by IH in heart (1.46-fold elevation in SA + IH compared with SA + IN group, P < 0.05) and by CS in lung (1.6-fold elevation in CS + IN compared with SA + IN group, P < 0.05), respectively. However, there was no synergistic or additive effect of IH and CS on E-FABP expression by both tissues. E-FABP mRNA expression levels were time-dependently increased after CS exposure, peaking at 28 day and starting to drop at 56 day. CONCLUSIONS: Our preliminary data suggested that IH and CS exert differential regulation on specific FABP expressions in rat heart and lung tissues, and that EFABP may serve as one of the biomarkers for the IH and/or CS-induced heart or lung injuries. Further studies are required to investigate the post-transcriptional changes of these FABP subtypes and the involved mechanisms.