Stem Cell Factor in Mast Cells and Increased Mast Cell Density in Idiopathic and Ischemic Cardiomyopathy

Abstract

Background-We compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (nϭ24) and ischemic cardiomyopathy (ICM) (nϭ10) undergoing heart transplantation and from control subjects (nϭ10) without cardiovascular disease. Methods and Results-HHMC density in DCM (18.4Ϯ1.6 cells/mm 2 ) and ICM (18.4Ϯ1.5 cells/mm 2 ) was higher than that in control hearts (5.3Ϯ0.7 cells/mm 2 ; PϽ.01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (r s ϭ.91; PϽ.001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca 2ϩ ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC 4 in patients with DCM and ICM compared with control subjects. Conclusions-Histamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C 4 ) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy. 1 Mast cells are present in human heart tissue 2,3 and in adventia and intima of coronary arteries of patients with coronary artery disease. [4][5][6] Moreover, the in vitro immunological activation of human heart tissue with anti-IgE induces the release of histamine and prostaglandin D 2 . 7,8 The concentration of histamine and the density of mast cells are increased in the arteries of cardiac patients, 4,5,9 and coronary arteries from cardiac patients are hyperresponsive in vitro to histamine. 4 Furthermore, in vivo administration of histamine and other mast cell-derived mediators (peptide LTC 4 ) in humans causes significant cardiovascular effects. 10 -12 Finally, serum IgE levels are increased in patients with coronary artery disease. 13,14 Taken together, these observations raise the possibility that local activation of cardiac mast cells might contribute, through the release of vasoactive mediators, to certain cardiovascular diseases. 15,16 Fibrosis is a hallmark of failing hearts in DCM and ICM. 17 The cells and the mediators responsible for fibroblast proliferation and collagen accumulation in failing hearts in DCM and ICM are largely unknown. Mast cells are involved in many types of inflammation and repair processes and are found in increased numbers in fibrotic tissues. For example, increased mast cell density has be...

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Allergy and the cardiovascular system

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“…Consequently, the cardiac tissue from patients with heart diseases contains and releases larger quantities of mast cell-derived mediators upon immunological and non-immunological activation [24]. These observations may contribute to explaining why cardiac manifestations of anaphylaxis are more severe in patients with ischaemic or degenerative heart diseases.…”

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