TY - JOUR T1 - <em>In-situ</em> metabolite profiling of remodeled arteries in Pulmonary Arterial Hypertension (PAH) using innovative mass spectrometry imaging (MSI) tools JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2015.PA4899 VL - 46 IS - suppl 59 SP - PA4899 AU - Sébastien J. Dumas AU - Raphael Legouffe AU - Fabien Pamelard AU - David Bonnel AU - Gaël Picard De Muller AU - Gregory Hamm AU - Peter Dorfmüller AU - Elie Fadel AU - Marc Humbert AU - Jonathan Stauber AU - Sylvia Cohen-Kaminsky AU - Alain Heron Y1 - 2015/09/01 UR - http://erj.ersjournals.com/content/46/suppl_59/PA4899.abstract N2 - PAH is associated to increased pulmonary arterial pressure, resulting in right heart failure and death. Understanding vascular remodeling pathways is a challenge for discovering novel therapeutic and diagnostic tools. Direct in-situ metabolite profiling of pulmonary arteries using MSI combined with the MultimagingTM analysis tool could be a pertinent strategy to better understand PAH pathways.Aims: 1) In-situ detection and quantification of metabolites in pulmonary arteries in order to determine the molecular signature of vascular remodeling.2) Assessment of MultimagingTM in the context of multiple comparisons of complex tissues.Human frozen lung samples from the tissue bank of the French Referral Center for PAH were cut in 10µm-thick sections and mounted onto conductive slides. Analysis was performed with a FTICR Mass Spectrometer at a 30 µm spatial resolution combined to the MultimagingTM analysis tool, allowing selection of areas containing vessels using contrast ions, and automated analysis of metabolites. Several metabolites showed differential levels between healthy and PAH samples with some m/z signals remaining to be characterized. Typical molecular signatures of the different types of vascular lesions were highlighted. For example, cADP (Cyclic ADP) ribose (key mediator of hypoxic pulmonary vasoconstriction) and ADP ribose, two metabolites belonging to the same pathway, were overexpressed in PAH lesions. MSI combined with MultimagingTM allowed the discovery of molecular signature of vascular remodeling in PAH. This strategy could open new avenues in understanding complex diseases on the basis of multiple tissue comparison. ER -