Deciphering atherosclerosis: unravelling spatial lipid heterogeneity through advanced MALDI-MSI profiling in rabbit aortic and human carotid artery plaques

Sphamandla Ntshangase; Shazia Khan; Taťana Gazarkova; Louise Bezuidenhout; Jakub Kaczynski; Stephanie Sellers; David Newby; Patrick Hadoke; Ruth Andrew

doi:10.1530/endoabs.94.P316

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Endocrine Abstracts (2023) 94 P316 | DOI: 10.1530/endoabs.94.P316

SFEBES2023 Poster Presentations Adrenal and Cardiovascular (78 abstracts)

Deciphering atherosclerosis: unravelling spatial lipid heterogeneity through advanced MALDI-MSI profiling in rabbit aortic and human carotid artery plaques

Sphamandla Ntshangase ¹ , Shazia Khan ¹ , Taťána Gazárková ² , Louise Bezuidenhout ¹ , Jakub Kaczynski ¹ , Stephanie Sellers ³ , David Newby ¹ , Patrick Hadoke ¹ & Ruth Andrew ¹

Err

Author affiliations

¹University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. ²University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. ³Centre for Heart Lung Innovation, St Paul’s Hospital and University of British Columbia, Vancouver, Canada

Atherosclerosis, a multifaceted cardiovascular disease characterised by fatty plaque buildup in large and medium-sized arteries, is a leading cause of heart attacks, strokes and peripheral arterial disease. Its global impact on morbidity and mortality rates poses a significant health challenge. This study aimed to comprehensively understand its complex pathogenesis using histologically aided Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to elucidate the spatial lipid profiles in rabbit atherosclerotic aortas and human carotid artery plaques. Rabbit aortas were harvested from male New Zealand White rabbits (aged 6-9 months, n=6) following double-balloon injury to the abdominal aorta and maintenance on a high-cholesterol diet (0.2%) to induce atherosclerosis. Human carotid artery plaques were collected ethically from NHS patients (men aged 50-80y n=5) undergoing Carotid Endarterectomy. MS images were co-registered with histopathological images to define important plaque features. Orthogonal Partial Least Squares for Discriminant Analysis (OPLS-DA) and variable importance in the projection (VIP) scores (>1.0 considered significant) were used to highlight potential markers and differences between plaque features. These include neointima and media in rabbit aortas, fibrous cap, and necrotic core in human plaques. The lesions were characterised by a high abundance of sphingomyelins, cholesterol esters and phosphatidylcholines, among other lipid classes. In both rabbit and human plaques, the most abundant lipid was sphingomyelin (34:1), observed in macrophage-rich regions, supporting their role in promoting lesion inflammation. Phosphatidylinositol (38:4) (VIP score=1.47) and phosphatidylcholine (34:2) (VIP score=1.91) distinctly differentiated rabbit aortas (media and neointima, respectively), whilst, in human plaques, phosphatidylcholine (34:2) (VIP score=1.45) and lysophosphatidylcholine (16:0) (VIP score=2.14) enriched the fibrous cap and necrotic core, respectively. This comparative study of an early-stage rabbit model and human pathology highlighted the translational relevance of animal models in atherosclerosis research while showcasing MALDI-MSI as a tool for spatial lipidomic profiling.