Molecular Mapping of Atherosclerotic Plaques with MALDI Mass Spectrometry Imaging

Atherosclerosis develops within heterogeneous arterial plaques. Here, even closely neighbouring regions can differ substantially in biological activity and potential vulnerability to rupture and thrombosis. Through matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) and especially MALDI imaging, these differences within the plaque can be studied while also preserving tissue architecture. With MALDI analysis, prepared tissue sections are converted into spatial molecular maps that show the differences in plaque chemistry across the arterial wall. These maps can be used to link changes in lipids and other biomolecules to regions affected by inflammation, necrosis, calcification and thrombosis. This narrative review, supported by a structured search of PubMed and PubMed Central from database inception to 14 September 2026, critically examines MALDI-based research in atherosclerosis across a translational continuum. The evidence base centres on spatial MALDI-MSI of plaque tissue, with non-imaging MALDI and orthogonal non-MALDI studies used as complementary context. Particular attention is given to the strength of evidence supporting proposed molecular signatures and to the distinction between exploratory findings and clinically validated applications. Integration of MALDI with histology, clinical imaging and emerging spatial-omics approaches could strengthen the biological interpretation of plaque-specific molecular signatures. However, methodological heterogeneity, incomplete molecular identification, small study populations and limited independent and prospective validation currently restrict translation into clinical practice.