Spatial transcriptomics elucidates localized immune responses in atherosclerotic coronary artery.

Atherosclerosis is characterized by the accumulation of lipids and immune cells in the arterial wall, leading to the narrowing and stiffening of blood vessels. Innate and adaptive immunity are involved in the pathogenesis of human atherosclerosis. However, spatial organization and roles of immune cells during disease progression remain poorly understood. A better understanding of the immune response's contribution to atherosclerosis progression could unveil novel therapeutic targets to mitigate plaque development and rupture, ultimately reducing cardiovascular events burden. Here, we utilised GeoMx® and CosMx™ technologies to analyse serial sections of human coronary arteries from patients with varying degrees of atherosclerotic lesion severity. Our work comprises a series of investigations and integrates findings from both datasets, including pathway analyses, cell typing, and neighbourhood analysis. This workflow highlights the power of combining these spatial transcriptomics platforms to elucidate biological processes at the single-cell level. Our approach unbiasedly identifies molecules and pathways of relevance to support the understanding of atherosclerosis pathogenesis and assess the potential for novel therapies.