Single cell analyses to understand the immune continuum in atherosclerosis

Abstract

Atherosclerosis is initiated by the accumulation of lipids in the arterial wall that trigger a complex and poorly understood network of inflammatory processes. At the same time, recent clinical findings reveal that targeting specific immune alterations in patients with cardiovascular disease (CVD) represents a promising approach to preventing recurrent cardiovascular events. In order to achieve these tailored therapies, it is critical to resolve the heterogenous environment of the atherosclerotic lesion and decipher the complex structural and functional changes which immune cells undergo throughout disease progression. Recently, single-cell approaches including single cell mass cytometry by time of flight (CyTOF), single cell RNA sequencing (scRNA-seq) and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) have emerged as valuable tools in resolving cellular plasticity within atherosclerotic lesions. In this review, we will discuss the most important insights that have been gleaned from the application of these single-cell approaches to validated experimental models of atherosclerosis. Additionally, as clinical progress in treatment of the disease depends on the translation of discoveries to human tissues, we will also examine the challenges associated with the application of single-cell approaches to human vascular tissue and the discoveries made by the initial efforts in this direction. Finally, we will analyze the advantages and limitations of dissociative single-cell approaches and how novel in-situ technologies could advance the field by allowing for the investigation of individual cells while preserving the heterogenous architecture of the atherosclerotic lesion.

Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis

“…Essentially, AS is caused by a series of cellular interactions. Multiple scRNA-seq data of plaques from mice and humans demonstrated the development of atherosclerosis resulting from the combined action of various types of cells ( 165 , 166 ). As described above, monocytes TEM plays a vital role in the development of AS.…”

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

“…Atherosclerosis is a disease associated with inflammation that relies heavily on the immune system for its development and modulation [ 28 ]. New high-throughput single cell technologies, such as mass cytometry and single-cell RNA sequencing, enable a comprehensive analysis of the immune system during atherosclerosis progression through uncovering the diversity of > 15 immune cell populations [ 29 – 31 ].…”

Immune Mechanisms of Plaque Instability

“…Plaque stability fundamentally depends on the level of inflammatory cell infiltration (49). Multidimensional single-cell RNA sequencing and mass cytometry of mouse and human atherosclerotic plaque have provided insights into the cellular landscape of atherosclerotic plaque at unprecedented granularity (50)(51)(52)(53)(54)(55), comprehensively reviewed in Hill et al (56). Although the relative frequency of immune cell populations varies between studies, macrophages and αβ T-cells consistently represent the most abundant cell types and overwhelming evidence supports their crucial role in atherosclerosis development and progression.…”