Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue using MALDI-ToF, ToF-SIMS and Hybrid SIMS

Sebastiaan van Nuffel (1) , Marceau Quatredeniers (2) , Alexander Pirkl (3) , Julia Zakel (3) , Jean-Pierre Le Caër (1) , Nicolas Elie (1) , Quentin Vanbellingen (1) , Sébastien Joël Dumas (2) , Morad Nakhleh (2) , Maria Rosa Ghigna (2) , Elie Fadel (2) , Marc Humbert (2) , Pierre Chaurand (4) , David Touboul (1) , Sylvia Cohen-Kaminsky (2) , Alain Brunelle (1, 5)

1 ICSN - Institut de Chimie des Substances Naturelles
2 HPPIT - Hypertension pulmonaire : physiopathologie et innovation thérapeutique
3 IONTOF GmbH
4 UdeM - Université de Montréal
5 LAMS - Laboratoire d'Archéologie Moléculaire et Structurale

Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15–60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z 885.6 as a marker of PAH in human lung tissue. The m/z 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.

Domaines: Chimie analytique

Sebastiaan van Nuffel, Marceau Quatredeniers, Alexander Pirkl, Julia Zakel, Jean-Pierre Le Caër, et al.. Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue using MALDI-ToF, ToF-SIMS and Hybrid SIMS. Analytical Chemistry, 2020, 92 (17), pp.12079. ⟨10.1021/acs.analchem.0c02815⟩. ⟨hal-02908467⟩