Single-cell immune landscape of human atherosclerotic plaques

Abstract

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Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

“…4a). The top three most upregulated genes in AC macrophages relative to PA macrophages - APOC1, FABP5 and APOE – all cluster together spatially in the AC-specific section of the UMAP plot and, concordant with recent findings, represent the anti-inflammatory macrophage foam cell subgroup as indicated by the high expression of APOC1 and APOE 13 (Extended Data Fig. 4c).…”

“…For example, in murine atherosclerotic aortas three distinct macrophage subsets were identified, including inflammatory, Res-like and TREM2hi macrophages 12 , enhancing our understanding of macrophage diversity within plaque. Additionally, immunophenotyping in carotid atherosclerosis revealed fundamental differences between T-cells and macrophages from symptomatic versus asymptomatic patients, including expansion of the CD4+ T-cell subset and macrophages with varied phenotypes in symptomatic patients 13 . However, these studies isolated specific cell lineages and excluded the site of disease – the vascular wall.…”

talklr uncovers ligand-receptor mediated intercellular crosstalk

“…Multiple cell-cell interactions can exist at the same time (e.g., A ->B and A-> C), and such one-to-many or many-to-many interactions are indeed known to occur frequently in the literature, as we will show later. Ligand-receptor interactions can be quantified using an interaction score: L i *R j , the product of expression levels for the ligand in cell type i and the receptor in cell type j 9,12 (Figure 1B). In talklr, we normalize interaction scores by dividing L i *R j with the sum of interaction scores across all possible states, so that normalized interaction scores sum up to 1 ( Figure 1C).…”

“…In the second approach, when both the ligand and the receptor are specifically enriched in one cell type (not necessarily the same cell type), a connection is drawn between this pair of cell types 7,8,11 . The third approach first quantifies ligand-receptor interactions by multiplying the expression level of the ligand in cell type i with the expression of the cognate receptor in cell type j to obtain an interaction score, and then prioritizes the ligand-receptor gene pairs with large interaction scores 9,12 .…”

Management of immune checkpoint inhibitor‐related adverse events: A review of case reports

“…Therefore, treatment with PD-1 inhibitors may have unanticipated consequences in cancer patients with underlying cardiovascular disease. 17 Most patients with inflammatory arthritis from ICIs were negative for rheumatoid factor and anticyclic citrullinated peptide antibodies traditionally associated with rheumatoid arthritis. 18 Treatment of inflammatory arthritis included nonsteroidal anti-inflammatory drugs (NSAIDs), prednisone, and both nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs).…”