Abstract

Mast cells are present in atherosclerotic lesions throughout their progression. The process of atherogenesis itself is characterized by infiltration and retention of cholesterol-containing blood-derived low-density lipoprotein (LDL) particles in the intimal layer of the arterial wall, where the particles become modified and ingested by macrophages, resulting in the formation of cholesterol-filled foam cells. Provided the blood-derived high-density lipoproteins (HDL) particles are able to efficiently carry cholesterol from the foam cells back to the circulation, the early lesions may stay stable or even disappear. However, the modified LDL particles also trigger a permanent local inflammatory reaction characterized by the presence of activated macrophages, T cells, and mast cells, which drive lesion progression. Then, the HDL particles become modified and unable to remove cholesterol from the foam cells. Ultimately, the aging foam cells die and form a necrotic lipid core. In such advanced lesions, the lipid core is separated from the circulating blood by a collagenous cap, which may become thin and fragile and susceptible to rupture, so causing an acute atherothrombotic event. Regarding the potential contribution of mast cells in the initiation and progression of atherosclerotic lesions, immunohistochemical studies in autopsied human subjects and studies in cell culture systems and in atherosclerotic mouse models have collectively provided evidence that the compounds released by activated mast cells may promote atherogenesis at various steps along the path of lesion development. This review focuses on the presence of activated mast cells in human atherosclerotic lesions. Moreover, some of the molecular mechanisms potentially governing activation and effector functions of mast cells in such lesions are presented and discussed.

Highlights

  • Mast cells are present in atherosclerotic lesions throughout their progression

  • Activated mast cells are present in human atherosclerotic lesions throughout the lesion development—i.e., from start to end

  • An association of elevated serum immunoglobulin E (IgE) antibody levels with the severity of coronary artery disease and with acute coronary events has been observed [136]. It is not known whether the mast cells in the human epicardial coronary arteries carry antigen-specific IgE bound to their surfaces, which is a central requirement for acute allergic reactions

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Summary

Atherogenesis—A Brief Outline of a Long Path of Events

Infiltration of circulating apolipoprotein(apo) B-containing lipoproteins, notably of the apoB-100—containing LDL particles, into the inner layer, the intima, of atherosclerosis-susceptible segments of the arterial tree is the root cause of atherogenesis Uptake of the modified cholesterol-containing LDL particles leads to accumulation in the macrophages of cholesterol as cholesteryl ester-containing cytoplasmic lipid droplets, thereby making the cells appear “foamy”. If the apoptotic foam cells are not effectively efferocytosed by their neighboring macrophages, they undergo post-apopotic secondary necrosis, whereupon the cytoplasmic cholesteryl ester droplets become displaced into the extracellular space of the intima, and, together with the remains of the dead macrophages form a necrotic lipid core [3,27,28]. The most significant and dangerous process in coronary atherosclerosis is the development of a fatty plaque, which often grows outward and fails cause chronic ischemic symptoms [32] Such non-obstructing lesions are characterized by an ever-growing necrotic lipid core accompanied with an ever-thinning fibrous cap, and they cause atherothrombotic complications often without warning [33]. The possible roles and relevance of mast cells in the pathogenesis of atherosclerosis, as briefly outlined above, will be presented and discussed

General Definition of Mast Cells and Their Functions
The Abdominal Aorta
Epicardial Coronary Arteries
Grading Mast Cell Activation in Human Atherosclerotic Coronary Arteries
Potential Mast Cell Triggers in Human Atherosclerotic Coronary Arteries
Mast Cells as Effector Cells in Atherogenesis
Actions Related to Early Atherogenesis
Actions Related to Advancing and Terminal Atherogenesis
Findings
Concluding Remarks
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