Vascular Macrophages in Atherosclerosis

Abstract

Atherosclerosis is the main pathological basis for the occurrence of most cardiovascular diseases, the leading global health threat, and a great burden for society. It has been well established that atherosclerosis is not only a metabolic disorder but also a chronic, sterile, and maladaptive inflammatory process encompassing both innate and adaptive immunity. Macrophages, the major immune cell population in atherosclerotic lesions, have been shown to play critical roles in all stages of atherosclerosis, including the initiation and progression of advanced atherosclerosis. Macrophages have emerged as a novel potential target for antiatherosclerosis therapy. In addition, the macrophage phenotype is greatly influenced by microenvironmental stimuli in the plaques and presents complex heterogeneity. This article reviews the functions of macrophages in different stages of atherosclerosis, as well as the phenotypes and functions of macrophage subsets. New treatment strategies based on macrophage-related inflammation are also discussed.

Ultrastructural Pathology of Atherosclerosis, Calcific Aortic Valve Disease, and Bioprosthetic Heart Valve Degeneration: Commonalities and Differences

“…The phenotyping of macrophages is mostly based on immunodetection methods such as immunostaining or flow cytometry upon fluorescence- or magnetic-activated cell sorting. Briefly, all macrophages are differentiated into pro-inflammatory (M1) and anti-inflammatory (M2), although this classification is oversimplified (at least for in vivo scenarios), and macrophages demonstrate a remarkable plasticity depending on the microenvironmental cues [ 38 , 39 , 40 , 41 ]. Although being widely established, this approach should ideally be combined with the ultrastructural interrogation of macrophages which also permits to identify their location and co-localisation with other plaque or valvular compartments.…”

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis

“…The effects of PS5 compound on the production of superoxide anion were analyzed in two cell types mostly involved in atherosclerotic disease: murine VSMCs (primary culture) and macrophages (RAW 264.7 cell line). It is well known that macrophages are the major immune cell population in the arterial plaques [51], while VSMCs contribute to vessel wall inflammation and lipoprotein retention, as well as to the formation of the fibrous cap responsible for the plaque stability [52]. Exploiting the ability of DHE probe to provide fluorescent signals upon the interaction with radical species, in the limits of a semiquantitative assay for the detection of the whole ROS content that changes continuously in a cell [53], in Figure 2 the confocal microscopy images of both cell types are reported.…”

Reduced SULT2B1b expression alleviates ox-LDL-induced inflammation by upregulating miR-148-3P via inhibiting the IKKβ/NF-κB pathway in macrophages

“…Anti-inflammatory and lipid metabolism-regulating drugs, such as canakinumab and statins, have become important strategies for the treatment of AS [ 4 ]. Up to now, although many disease-causing factors have been shown to be associated with the development of AS, oxidized low-density lipoprotein (ox-LDL) remains a very important risk factor for inducing macrophages to express many inflammatory molecules, especially pro-inflammatory cytokines, which can further promote AS development [ 5 – 7 ]. AS is also considered to be a chronic inflammatory disorder, and growing evidence has shown the critical roles of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α), which exhibit their unique functions during the progression of AS [ 8 , 9 ].…”