Editorial M ast cells feel the strain *

See article by Huang et al. [1] (pages 150 –160) in this cytokines, prostanoids, platelet activators, vasoactive issue. agents and growth factors [8]. Mast cell activation may also have a role to play in the Mast cells are implicated to be involved in the pathoinitiation and progression of heart disease. Histamine has genesis of atherosclerosis and acute coronary syndromes. been shown to promote vascular smooth muscle cell However, the contribution of mast cells in the initiation of growth, and blockade of H -receptors has been shown to 1 atherogenic mechanisms, and the role of mediators they reduce intimal thickening in a mouse model of vascular release is not fully understood. In this issue of Carinjury [9,10]. It has been demonstrated that mast cell diovascular Research, Huang et al. [1] provide evidence degranulation can induce apoptosis of rat cardiomyocytes that mast cells can contribute to stress related cardiac and stimulate proliferation of non-myocardial cells, a disease. They showed that mast cells become activated in situation that would lead to the progression of myocardial response to acute restraint stress in mice. This effect was fibrosis and a loss in contractile function [11]. This effect enhanced in ApoE knock-out mice. These mice were seen was attributable to the protease action of rat mast cell to have higher levels of histamine and a greater number of chymase. In a study examining coronary arteries obtained mast cells, compared to wild type. The findings provide from patients at autopsy, a 5–10-fold increase in mast cell important evidence that acute coronary syndromes can be numbers in cap, core and shoulder regions of atherosmediated by neuroinflammatory reactions. clerotic lesions were observed. In the shoulder region, 85% Mast cells are found within every major organ of the of the mast cells were activated [12]. Chymase and body. Within the heart they can be localised to the tryptase released by mast cells may destabilise atheromatus interstitial space between myocytes, generally in regions plaques due to their action on the extracellular matrix. associated with the coronary arteries [2]. Mast cells are Both chymase and tryptase can directly activate matrix also found within media and adventitia of the coronary metalloproteinases (MMPs), cleave and activate procolvessels, with the majority residing in adventitia [3]. Mast lagenase, or stimulate the release of TNF-a which in turn cell numbers have been shown to increase during heart activate macrophages to secrete MMPs [7,13,14]. failure, with great numbers found in patients with The contents of mast cells may have an important role to idopathic and ischaemic cardiomyopathy [4]. Greater play in coronary artery vasoconstriction associated with numbers of mast cells are also associated with the shoulder acute coronary syndromes. Intra-coronary injections of region of atherosclerotic plaques [5]. Those coronary histamine have been shown to induce vasoconstriction of vessels that are associated with myocardial infarction have atherosclerotic segments of the artery, but not in nonbeen shown to increase their numbers of degranulated mast diseased regions [15,16]. Indeed, histamine has been cells within the adventitia of regions associated with shown to act as a ‘double agent’ in human arteries, plaque rupture. Within atherosclerotic lesions mast cells producing both relaxation and contraction [17]. The senare associated with activated complement, T-lymphocytes sitivity of atherosclerotic regions of the vessel wall is most and macrophages [6,7]. Mast cells release a repertoire of likely due to either endothelial dysfunction at these sites, atherogenic mediators including proteases, chemokines, and/or up-regulation of histaminergic receptors in spastic areas of diseased coronary arteries. Other vasoactive agents released by mast cells, namely prostaglandin D and 2 leukotriene C will also contribute to the contractile effects *Tel.: 144-1895-828-727; fax: 144-1895-828-900. 4 E-mail address: [email protected] (A.H. Chester). of histamine. It has been shown that leukotriene C4