Mast cells in vulnerable atherosclerotic plaques – a view to a kill

Abstract

The aim of the present review is to discuss the participation of mast cells in the pathogenesis of erosion and rupture of atherosclerotic plaques, the major causes behind acute coronary syndromes and myocardial infarction. We present ex vivo observations describing mast cells and their activation in human atherosclerotic plaques and discuss in vitro and in vivo data showing that mast cells are potential regulators of inflammation, immunity and adverse remodeling, including matrix remodeling and cell death. Furthermore, we focus on studies that have been performed with human tissues and human mast cells, but when appropriate, we also discuss observations made in animal models. Finally, we present potential pharmacological means to modulate mast cell responses in the arterial vessel walls.

Mast cells promote atherosclerosis by inducing both an atherogenic lipid profile and vascular inflammation

“…Recent in vivo data using apoE À/À and ldlr À/À /Kit W-sh/W-sh mice support the in vitro concept that mast cells participate in the pathogenesis of atherosclerosis by inducing vascular leakage, lipid accumulation, CXCR2/VLA-4-mediated recruitment of leukocytes, intraplaque hemorrhage, macrophage apoptosis, and by releasing proinflammatory cytokines, such as IL-6 and interferon-g (IFN-g) [Bot et al, 2007;Lindstedt et al, 2007;Sun et al, 2007]. However, despite increased mast cell-mediated deposition of lipids in the aortic arch and the thoracic-abdominal aortas in mast cellcompetent ldlr À/À mice, no significant differences have been observed in the levels of plasma lipids and lipoproteins [Sun et al, 2007].…”

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

“…A link between MC activation and atherosclerosis has now been clearly demonstrated [4,36] as their numbers are greatly increased in the intima at sites of arterial plaque rupture [36], in advanced plaque lesions in the carotid artery [37], and patients who died of acute myocardial infarction have an increased number of degranulated MCs at the actual site of plaque erosion or rupture [38]. Therapies aimed at treating atherosclerosis include Niacin which blocks vascular inflammation, ROS, and inflammatory cytokine production in conjunction with diminishing NF-ĸB activation [39].…”

Mast Cells Induce Vascular Smooth Muscle Cell Apoptosis via a Toll-Like Receptor 4 Activation Pathway

“…5 Besides macrophages and T lymphocytes, there is accumulating evidence that mast cells (MCs) are also important mediators in determining the phenotype of an atherosclerotic plaque. 6,7 Activated MCs may contribute to vulnerable plaque formation via different mechanisms. Bot et al 8 showed that MCs can induce plaque destabilization in a murine model for atherosclerosis, associated with an increase in intraplaque hemorrhaging because of enhanced vascular permeability and enlargement of the lipid-rich necrotic core because of macrophage apoptosis.…”