Increased Number of Mast Cells in Atherosclerotic Lesions Correlates with the Presence of Myeloid but not Plasmacytoid Dendritic Cells as well as Pro-inflammatory T Cells

Abstract

Overall, the higher number of mast cells in plaques, particularly with unstable morphology, suggests that mast cells might be involved in the progression of atherosclerosis. The correlation of mast cells with other immune cells that are pivotal in atherogenesis, e.g., myeloid dendritic cells and pro-inflammatory T cells, also suggests an interplay leading to plaque destabilization. Therefore, modulating local mast cell function and invasion into the plaque might be a therapeutic tool for plaque stabilization.

Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding

“…Thus, when compared with normal human aortas, the expression of cathepsin G and chymase in atherosclerotic aortas was found to be increased [39]. In line with the above observation, human atherosclerotic lesions have been shown to contain significantly higher numbers of cathepsin G-positive MCs compared to control vessels [40]. In a previous immunohistochemical study [34], we compared the proportions of two cathepsin G-containing cells, MCs and neutrophils, in atherosclerotic lesion of human coronary artery, and found a MC-to-neutrophil ratio of 5: 1.…”

Dendritic Cells and T Cells, Partners in Atherogenesis and the Translating Road Ahead

“…In addition to DCs, other cell types, such as inflammatory T cells and master cells in atherosclerotic lesions, also correlate with disease severity, indicating a complex interplay of different cell types for plaque destabilization. Therefore, modulating the interaction of local T cells with other immune cells and preventing their invasion into the plaque might be a therapeutic tool for plaque stabilization (162). Consistently, accumulating evidence indicates that on evaluation of the feasibility of DCs and T cells as a diagnostic tool, the subsets of blood CD4 + , CD8 + , and CD4 + CD25 + Foxp3 + T cells and the ratio of CD4 to CD8 cells hold promise as biomarkers of coronary artery disease (163).…”

Cellular and Molecular Mechanisms of Mast Cells in Atherosclerotic Plaque Progression and Destabilization

“…The effects of other chronic disorders on the characterization of plaques in terms of cellularity and immune responses remain unclear [ 90 ] > > > What is the relevance of MC interactions with DCs in the formation of atherosclerotic plaques? Investigation of the cellular crosstalk between MCs and other plaque infiltrating cells with atherogenic activity like myeloid DCs may provide more details on how MCs involve the pathology of the disease [ 91 ] > > > How does MC depletion or silencing affect the course of atherosclerosis? Disrupting KIT signaling using tyrosine kinase inhibitors (TKIs) including imatinib affects the late stage of MC differentiation and depletes MCs.…”