Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

Abstract

Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

Figure 1

Adhesion (a) and penetration (b, c) of blood monocytes into the intima of the human aorta. Scanning Electron Microscopy (SEM). Scale bars = 15 μm (a) and 5 μm (b, c).

Figure 2

The presence of modified LDL, labelled with gold particles (arrows), in lysosomes of macrophages, visualized in an in vitro experiment. Transmission Electron Microscopy (TEM). Scale bar = 600 nm.

Figure 3

Foam cells of macrophage origin in an atherosclerotic lesion of the human aorta (a, b). (a) CD68+ cells (brown), some of which display a typical foam cell appearance (arrows). Immunohistochemistry; peroxidase-anti-peroxidase (PAP) technique; counterstain with Mayer's hematoxylin. (b) A large number of lipid inclusions (“lipid droplets”) (L) that fill practically all the cytoplasm in a foam cell in a human atherosclerotic plaque. Ly: lysosome; N: nucleus. TEM. Scale bars = 100 μm (a) and 2 μm (b).