March 17, 1998Circulation244 citations
View Full PaperStem Cell Factor in Mast Cells and Increased Mast Cell Density in Idiopathic and Ischemic Cardiomyopathy
Key Result
Cardiac mast cell density was significantly higher in patients with idiopathic dilated and ischemic cardiomyopathy (18.4 cells/mm2) compared to controls (5.3 cells/mm2; P<.01).
Study Design
Type
Observational (n=44)
Structured PICO
Does cardiac mast cell density and mediator release differ in patients with idiopathic and ischemic cardiomyopathy compared to controls?
P
Population
44 subjects, including patients with idiopathic dilated cardiomyopathy (DCM) (n=24) and ischemic cardiomyopathy (ICM) (n=10) undergoing heart transplantation, and control subjects (n=10) without cardiovascular disease.
C
Comparator
Control subjects without cardiovascular disease (n=10)
O
Outcome
Cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators (histamine, tryptase, LTC4)surrogate
Mast cell density and mediator release are significantly increased in failing hearts from patients with DCM and ICM, suggesting a potential role in cardiac fibrosis and remodeling.
Main Result
Absolute Event Rate: 18.4% vs 5.3%
p-value: p=<.01
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) (n=24) and ischemic cardiomyopathy (ICM) (n = 10) undergoing heart transplantation and from control subjects (n = 10) without cardiovascular disease. METHODS AND RESULTS: HHMC density in DCM (18.4+/-1.6 cells/mm2) and ICM (18.4+/-1.5 cells/mm2) was higher than that in control hearts (5.3+/-0.7 cells/mm2; P<.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)=.91; P<.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 (Ca2+ 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 LTC4 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 C4) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy.