Spatial lipidomic profiles of atherosclerotic plaques: A mass spectrometry imaging study

Abstract

Lipids contribute to atherosclerotic cardiovascular disease but their roles are not fully understood. Spatial lipid composition of atherosclerotic plaques was compared between species focusing on aortic plaques from New Zealand White rabbits and carotid plaques from humans (n = 3), using matrix-assisted laser desorption/ionization mass spectrometry imaging. Histologically discriminant lipids within plaque features (neointima and media in rabbits, and lipid-necrotic core and fibrous cap/tissue in humans) included sphingomyelins, phosphatidylcholines, and cholesteryl esters. There were 67 differential lipids between rabbit plaque features and 199 differential lipids in human, each with variable importance in projection score ≥1.0 and p < 0.05. The lipid profile of plaques in the rabbit model closely mimicked that of human plaques and two key pathways (impact value ≥ 0.1), sphingolipid and glycerophospholipid metabolism, were disrupted by atherosclerosis in both species. Thus, mass spectrometry imaging of spatial biomarkers offers valuable insights into atherosclerosis.

Keywords: Atherosclerosis; Cardiovascular lipid biomarkers; Histology; Mass spectrometry imaging; Spatial lipidomics.