Macrophages and T cells in atherosclerosis: a translational perspective

Abstract

Atherosclerosis is now considered a chronic maladaptive inflammatory disease. The hallmark feature in both human and murine disease is atherosclerotic plaques. Macrophages and various T-cell lineages play a crucial role in atherosclerotic plaque establishment and disease progression. Humans and mice share many of the same processes that occur within atherogenesis. The various similarities enable considerable insight into disease mechanisms and those which contribute to cardiovascular complications. The apolipoprotein E-null and low-density lipoprotein receptor-null mice have served as the foundation for further immunological pathway manipulation to identify pro- and antiatherogenic pathways in attempt to reveal more novel therapeutic targets. In this review, we provide a translational perspective and discuss the roles of macrophages and various T-cell lineages in contrasting proatherosclerotic and atheroprotective settings.

Galectin-9: A Suppressor of Atherosclerosis?

“…Several types of immunoreactive cells are present throughout atherosclerosis formation including macrophages, T cells, B cells, mast cells and dendritic cells ( Figure 1 ). Despite the macrophages are the key cells in atherosclerosis ( 6 ), T cells are shown to be concerned with atherogenesis and especially T-cell subpopulations are suggested to trigger/dampen atherosclerotic inflammatory processes ( 7 ). Previous studies have showed that the pathogenesis of atherosclerosis is characterized by an imbalance between T-helper 1 (Th1) - and Th2-mediated immune functions ( 8 ).…”

“…In contrast, Th2-biased responses antagonize proatherogenic Th1 functions and thereby confer atheroprotection. Indeed, the role of the Th2 cells in the atherosclerotic process remains controversial and depends on the stage and site of the atherosclerotic lesion ( 7 , 12 ). The vast majority of studies have shown interleukin- (IL-) 17 contributed to the proinflammatory milieu of atherosclerosis ( 13 – 15 ).…”

<p>Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions</p>

“…T cells are among the first cells to be recruited into atherosclerotic lesion. [79][80][81][82] The adaptive response is based on CD4 + and CD8 + T cells activation and antibody secretion by B cells. Once activated, CD4+ T cells multiply and differentiate into specialized effector T helper (Th) lymphocytes, while activated CD8+ T cells multiply and differentiate into cytotoxic CD8+ T lymphocytes.…”

“…Th17 cells produce IL-17 which has different effects on lesions, emphasizing endothelial inflammation but also increasing fibrosis and promoting plaque stability. [79][80][81][82] Treg cells are immunoregulatory cells with atheroprotective properties: they secrete the immunosuppressive cytokines such as transforming growth factor-beta (TGF-β), IL-10 and IL-35, which exert anti-inflammatory actions. 83…”

Functional subsets of circulating follicular helper T cells in patients with atherosclerosis

“…Atherosclerosis is responsible for several adverse and deadly vascular events such as coronary artery disease (CAD), myocardial infarction, and stroke (Bartlett et al., 2019). Activation or injury of endothelium is suggested to happen early in the course of the events (Mitra et al., 2017).…”