Mast cells have been associated with arteriogenesis and collateral formation. In advancedhuman atherosclerotic plaques, mast cells have been shown to colocalize with plaque neovessels,and mast... Show moreMast cells have been associated with arteriogenesis and collateral formation. In advancedhuman atherosclerotic plaques, mast cells have been shown to colocalize with plaque neovessels,and mast cells have also been associated with tumor vascularization. Based on these associations,we hypothesize that mast cells promote angiogenesis during ischemia. In human ischemic muscletissue from patients with end-stage peripheral artery disease, we observed activated mast cells,predominantly located around capillaries. Also, in mouse ischemic muscles, mast cells were detectedduring the revascularization process and interestingly, mast cell activation status was enhanced up to10 days after ischemia induction. To determine whether mast cells contribute to both arteriogenesisand angiogenesis, mast cells were locally activated immediately upon hind limb ischemia in C57Bl/6mice. At day 9, we observed a 3-fold increase in activated mast cell numbers in the inguinal lymphnodes. This was accompanied by an increase in the amount of Ly6Chigh inflammatory monocytes.Interestingly, local mast cell activation increased blood flow through the hind limb (46% at day 9)compared to that in non-activated control mice. Histological analysis of the muscle tissue revealedthat mast cell activation did not aect the number of collaterals, but increased the collateral diameter,as well as the number of CD31+ capillaries. Together, these data illustrate that locally activated mastcell contribute to arteriogenesis and angiogenesis. Show less
Hermans, M.; Roeters van Lennep, J.E.; Daele, P. van; Bot, I. 2019
Mast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which... Show moreMast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which is a hematological disease that is characterized by the accumulation of mast cells due to clonal proliferation. This association suggests an important role for mast cells in cardiovascular disease. Indeed, the evidence establishing the contribution of mast cells to the development and progression of atherosclerosis is continually increasing. Mast cells may contribute to plaque formation by stimulating the formation of foam cells and causing a pro-inflammatory micro-environment. In addition, these cells are able to promote plaque instability by neo-vessel formation and also by inducing intraplaque hemorrhage. Furthermore, mast cells appear to stimulate the formation of fibrosis after a cardiac infarction. In this review, the available data on the role of mast cells in cardiovascular disease are summarized, containing both in vitro research and animal studies, followed by a discussion of human data on the association between cardiovascular morbidity and diseases in which mast cells are important: Kounis syndrome, mastocytosis and allergy. Show less
The presence of mast cells in human atherosclerotic plaques has been associated with adverse cardiovascular events. Mast cell activation, through the classical antigen sensitized-IgE binding to... Show moreThe presence of mast cells in human atherosclerotic plaques has been associated with adverse cardiovascular events. Mast cell activation, through the classical antigen sensitized-IgE binding to their characteristic Fcε-receptor, causes the release of their cytoplasmic granules. These granules are filled with neutral proteases such as tryptase, but also with histamine and pro-inflammatory mediators. Mast cells accumulate in high numbers within human atherosclerotic tissue, particularly in the shoulder region of the plaque. These findings are largely based on immunohistochemistry, which does not allow for the extensive characterization of these mast cells and of the local mast cell activation mechanisms. In this study, we thus aimed to develop a new flow-cytometry based methodology in order to analyze mast cells in human atherosclerosis. We enzymatically digested 22 human plaque samples, collected after femoral and carotid endarterectomy surgery, after which we prepared a single cell suspension for flow cytometry. We were able to identify a specific mast cell population expressing both CD117 and the FcεR, and observed that most of the intraplaque mast cells were activated based on their CD63 protein expression. Furthermore, most of the activated mast cells had IgE fragments bound on their surface, while another fraction showed IgE-independent activation. In conclusion, we are able to distinguish a clear mast cell population in human atherosclerotic plaques, and this study establishes a strong relationship between the presence of IgE and the activation of mast cells in advanced atherosclerosis. Our data pave the way for potential therapeutic intervention through targeting IgE-mediated actions in human atherosclerosis. Show less
Atherosclerosis is a chronic inflammatory disease in which lipids and cells of the immune system accumulate in the vessel wall. Clinical complications, such as a myocardial infarction or stroke may... Show moreAtherosclerosis is a chronic inflammatory disease in which lipids and cells of the immune system accumulate in the vessel wall. Clinical complications, such as a myocardial infarction or stroke may occur when advanced atherosclerotic lesions become unstable and rupture. In this thesis, the influence of the psychological stress response and stress-related neuropeptides on vascular inflammation and atherosclerotic lesion development has been investigated. We demonstrated that acute stress results in activation of a potent type of immune cell in the vessel wall, the mast cell, leading to increased inflammation and atherosclerotic plaque destabilization. Furthermore, we have shown that (peri)vascular mast cell activation leads to neutrophil recruitment, thus aggravating the local inflammatory response. In addition, we demonstrated increased expression of neuropeptide Y in advanced atherosclerotic lesions and that overexpression of this peptide results in increased lesion development. These insights emphasize a contributing role for psychological stress to atherosclerotic lesion development and as a risk factor for acute cardiovascular syndromes and opens up new avenues for possible future anti-inflammatory therapies to reduce the risk of cardiovascular disease. Show less
Suurmond, J.; Heemst, J. van; Heiningen, J. van; Dorjee, A.L.; Schilham, M.W.; Beek, F.B. van der; ... ; Toes, R.E.M. 2013
