Spatial Transcriptomic Approach to Understanding Coronary Atherosclerotic Plaque Stability

作者：Maria Gabriela Gastanadui, Camilla Margaroli, Silvio Litovsky, Robert P. Richter, Dezhi Wang, Dongqi Xing, J. Michael Wells, Amit Gaggar, Vivek Nanda, Rakesh P. Patel, Gregory A. Payne · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2024 · DOI：10.1161/atvbaha.123.320330 · 被引用次数：52 · 研究领域：Single-cell and spatial transcriptomics、Atherosclerosis and Cardiovascular Diseases、Cardiac Fibrosis and Remodeling

BACKGROUND: Coronary atherosclerotic plaques susceptible to acute coronary syndrome have traditionally been characterized by their surrounding cellular architecture. However, with the advent of intravascular imaging, novel mechanisms of coronary thrombosis have emerged, challenging our contemporary understanding of acute coronary syndrome. These intriguing findings underscore the necessity for a precise molecular definition of plaque stability. Considering this, our study aimed to investigate the vascular microenvironment in patients with stable and unstable plaques using spatial transcriptomics. METHODS: Autopsy-derived coronary arteries were preserved and categorized by plaque stability (n=5 patients per group). We utilized the GeoMx spatial profiling platform and Whole Transcriptome Atlas to link crucial histological morphology markers in coronary lesions with differential gene expression in specific regions of interest, thereby mapping the vascular transcriptome. This innovative approach allowed us to conduct cell morphological and spatially resolved transcriptional profiling of atherosclerotic plaques while preserving crucial intercellular signaling. RESULTS: We observed intriguing spatial and cell-specific transcriptional patterns in stable and unstable atherosclerotic plaques, showcasing regional variations within the intima and media. These regions exhibited differential expression of proinflammatory molecules (eg, IFN-γ [interferon-γ], MHC [major histocompatibility c...