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Intrauterine growth restriction (IUGR) is associated with increased morbidity and metabolic anomalies in adults. The serum proteome of venous blood was compared in 43 IUGR and 45 adequate gestational age (AGA) infants, separated into three gestational age groups, “Very Preterm” 29–32 weeks, “Moderate Preterm” 33–36 w, and, “Term” ≥ 37 weeks, in samples drawn three times from birth to 1 month of life. After depleting the abundant serum proteins (ProteoMiner TM ), expression changes were studied by 2-DE, image analysis (Proteomweaver 4.0 TM ), and identification by MALDI-TOF/TOF. Significant expression differences were found in thirty-four proteins, and thirty-three were identified. Lysophospholipid acyltransferase 7 (MBOAT7), was detected exclusively in IUGR of all gestational ages and sampling times; seven other proteins were found only in AGA. Another twenty-five proteins had intensity changes ≥ 2.5 folds in IUGR: twenty were upregulated and five downregulated. Western blots confirmed the identification of several proteins: MBOAT7 increased 20.5-fold in IUGR, while AGA had 11.2-fold higher levels of SUMO3 and sumoylated proteins and 13.7-fold higher levels of APOL1. Upregulation of MBOAT7 in IUGR neonates could be an adaptive response to protect the brain from an adverse environment. Biological significance There are significant protein expression differences between IUGR and AGA at different gestational age groups and blood extraction times. The extensive upregulation of lysophospholipid acyltransferase 7 in all IUGR gestational ages and extraction times might be an adaptative response to an adverse fetal environment, reminiscent of Barker's fetal programming theory. Two serotransferrins were also upregulated in IUGR of all gestational ages. Just at birth “Very Preterm” IUGR showed nine upregulated proteins, including five albumins, apolipoprotein E, keratin type I cytoskeletal 10, solute carrier family member 2 fragment, and anaphase-promoting complex subunit 2.

To examine whether differentially expressed proteins are present in the serum of patients with obstructive sleep apnoea (OSA), iTRAQ techniques (isobaric tags for relative and absolute quantification) were employed in a prospective study. Individuals were assigned to either a non-OSA control group (apnoea-hypopnoea index, AHI5) or an OSA group (AHI ≥5). Blood samples were collected, aliquoted and frozen at -80 °C. Protein digestion and tagging with iTRAQ4plex® and mass spectrometry analysis was then performed (MALDI TOF/TOF). Ten male subjects were included in the control group (age = 45 ± 9.7 years) and 30 male patients in the OSA group (age = 45 ± 10.7 years), the latter being then subdivided into three severity groups. A total of 103 proteins were identified with differential levels between patients with OSA and controls. Of these, 11 proteins were underexpressed and 19 were overexpressed in patients with OSA. C4BPA and thrombospondin were underexpressed in all three OSA severity groups. Among the overexpressed proteins, 13 were overexpressed in the mild OSA group, seven in the moderate group and five in the severe group. Analysis of interactions between the identified proteins revealed that protein alterations in OSA are primarily associated with derangements in lipid and vascular metabolic pathways. This study provides initial evidence that differential protein expression occurs in adults with OSA, and that such proteins change according to disease severity, and appear to primarily involve lipid and vascular metabolic pathways.

The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress. We studied 69 consecutive patients referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea-hypopnoea index (AHI) ≥ 5) and without (AHI < 5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy. We included 46 OSA patients (mean ± sd AHI 49 ± 32.1) and 23 non-OSA subjects (AHI 3 ± 0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels. In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.