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Altered Metabolic Profile in Congenital Lung Lesions Revealed by 1H Nuclear Magnetic Resonance Spectroscopy

DOI: 10.1155/2014/391836

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Abstract:

Congenital lung lesions are highly complex with respect to pathogenesis and treatment. Large-scale analytical methods, like metabolomics, are now available to identify biomarkers of pathological phenotypes and to facilitate clinical management. Nuclear magnetic resonance (NMR) is a unique tool for translational research, as in vitro results can be potentially translated into in vivo magnetic resonance protocols. Three surgical biopsies, from congenital lung malformations, were analyzed in comparison with one control sample. Extracted hydrophilic metabolites were submitted to high resolution 1H NMR spectroscopy and the relative concentration of 12 metabolites was estimated. In addition, two-dimensional NMR measurements were performed to complement the results obtained from standard monodimensional experiments. This is one of the first reports of in vitro metabolic profiling of congenital lung malformation. Preliminary data on a small set of samples highlights some altered metabolic ratios, dealing with the glucose conversion to lactate, to the relative concentration of phosphatidylcholine precursors, and to the presence of myoinositol. Interestingly some relations between congenital lung lesions and cancer metabolic alterations are found. 1. Introduction Lung development is a highly regulated and coordinated process, typified by stage specific changes in structure and function, which includes branching morphogenesis, angiogenesis, sacculation, alveologenesis, and cytodifferentiation [1]. Congenital pulmonary disease is characterized by a wide variety of abnormalities arising at different stages of the process [2]. Metabolomics is an emerging approach that uses analytical techniques, such as nuclear magnetic resonance (NMR) [3] spectroscopy, or mass spectrometry (MS) [4], to achieve a comprehensive global monitoring of metabolites and their fluctuations in response to various stimuli. Although gene/protein expressions schemes provide useful clues to organs development and function, many factors like posttranslational modifications, alternative gene functions, or compartmentalization also raise important biochemical changes. Therefore, metabolic profiling is essential to completely describe the physiopathological state of a biological system. Considerable efforts in this sense were devoted to human lung cancer [5, 6] and to human lung injury [7], but very limited information is available about metabolic perturbations arising in situ from congenital lung malformations. The purpose of this study was to determine the feasibility of tissue extraction and

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