Correlation Between Mast Cell Density and Myocardial Fibrosis in Congestive Heart Failure Patients

Abstract

Besides the well-established role of mast cells in allergic reactions as an important source of vasoactive and proinflammatory products, they have been related to tissue fibrosis and remodelling processes. In a heart failure (HF) animal model, mast cells were shown to synthesize transforming growth factor β1 and basic fibroblast growth factor in myocardial tissue and were localized to an area with fibrosis. Our objective was to quantify mast cell density in left ventricles from patients with congestive heart failure who were candidates for transplantation and to analyze whether they showed a correlation with the fibrosis level of the same area. Methods We obtained myocardial biopsies from 20 patients with end-stage HF secondary to idiopathic dilated cardiomyopathy (iDCM) undergoing heart transplantation and 15 controls (donors without cardiopathy). Mast cells were detected by immunohistochemistry with a human mast cell chymase antibody and fibrosis levels measured with picrosirius red staining of collagen fibrils with later quantification by morphometry. Results The patients mean age was 51 ± 3 years. Fibrosis levels in the myocardial sections from patients with congestive HF was three-fold higher than those in control myocardium (12.41 ± 1.7% vs 3.98 ± 0.63%, P < .001). Mast cell density correlated with the collagen fraction and could be fitted to a linear regression curve: collagen fraction = 0.78 + 0.05 mast cell density ( n = 33, P < .005, R 2 = 0.28). Conclusion The elevated collagen fraction present in failing hearts may be the cause of increased stiffness and loss of elasticity that is detected in patients with end-stage HF. Due to the mast cells capacity to synthesize vasoactive and fibrogenic products and the correlation between their density and fibrosis levels, they probably play a role in the ventricular remodelling in HF.