Endocrine Abstracts

Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disorder characterised by the gradual build-up of plaques in the arterial wall. Unstable plaques are more dangerous than stable plaques as they are prone to rupture and obstruct blood flow, resulting in heart attacks and strokes. Lipids play a key role in plaque progression, yet their exact involvement remains elusive. We hypothesise that stable or unstable plaques will have distinct spatial lipid phenotypes. We sought to characterise the spatial lipid composition of atherosclerotic plaques. Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) was used for spatial lipidomic profiling of rabbit and human plaques. Rabbit aortic plaques were harvested from male New Zealand White rabbits (aged 6-9 months, n=6) following double-balloon injury to the abdominal aorta and maintained on a high-cholesterol diet (0.2%) to induce atherosclerosis under Home Office guidance. Carotid endarterectomy specimens were collected from symptomatic NHS Lothian patients (men aged 50-80y, n=6) with ethical approval. MS images were co-registered with histopathological images (hematoxylin and eosin, alizarin red, CD68, α-smooth muscle actin) to reveal the metabolic and spatial information associated with ASCVD. Unique histologically-discriminant lipids were identified in rabbit and human plaques, including sphingomyelins, phosphatidylcholines, cholesteryl esters, triglycerides, and oxidised phospholipids, among others. MSI enabled mapping of lipid/lipid classes that define histologically important regions such as the lipid-necrotic core, fibrous tissue and macrophage-rich regions. In both rabbit and human plaques, relatively high levels of sphingomyelins were observed in macrophage-rich regions, supporting their central role in promoting lesional inflammation, while glycerophosphocholines were among the lipids enriched in the lipid-necrotic core. The lipid profile in a rabbit model mimics that observed in human carotid plaques, serving as a good model for early-stage ASCVD. Important pathophysiological plaque features that define plaque (in)stability can be distinguished based on their lipid signatures using MSI.