Effects of mast cells on the behavior of isolated heart fibroblasts: Modulation of collagen remodeling and gene expression

Abstract

The extracellular matrix plays a critical role in the development and maintenance of the vertebrate heart. Changes in the accumulation, composition, or organization of the extracellular matrix are known to deleteriously affect heart function. Mast cells are thought to stimulate collagen expression and fibroblast proliferation accompanying fibrosis in some organs; however, the effects of mast cells on the heart interstitium are largely unexplored. The present studies were carried out to determine the effects of mast cells on isolated heart fibroblasts. Several in vitro assays were used including collagen gel contraction to examine the effects of mast cells on the function of isolated fibroblasts. Neonatal heart fibroblasts were cultured either with mast cells, mast cell-conditioned medium, or mast cell extracts, and their ability to contract collagen gels measured. Results from these experiments indicated that mast cells inhibit heart fibroblast migration and contraction of 3-dimensional collagen gels. Further experiments indicated that incubation of neonatal heart fibroblasts with extracts of mast cells altered the expression of collagen, matrix metalloproteases, and matrix receptors of the integrin family. These studies suggest that mast cells play an important role in the regulation of the cardiac interstitial matrix. Further studies are warranted to determine the mechanisms whereby mast cells modulate fibroblast activity.

Rat cardiac mast cell maturation and differentiation following acute ventricular volume overload

“…These acute changes in cardiac mast cell morphology occur concurrently with remodeling of the extracellular matrix [3][4][5]16]. Cardiac mast cell degranulation can also produce an acute depression in left ventricular function, development of myocardial edema, matrix metalloproteinase activation, reductions in collagen concentration, and alterations in fi broblast contraction [16][17]. While it is now clear that these activated mast cells are capable of mediating extracellular matrix degradation [1,4], the origin of these additional mast cells in the myocardium remains in question.…”

Influence of Mast Cells on Structural and Functional Manifestations of Radiation-Induced Heart Disease

“…Some of these mediators are preformed and stored in granules ready for immediate release, whereas others are synthesized on demand (22). Possible explanations for how mast cells may affect connective tissue deposition and/or degradation include altered expression of procollagens and matrix metalloproteinases by cardiac fibroblasts (39,40); formation of heparin and transforming growth factor-h; formation of chymases, which generate the profibrogenic hormone angiotensin II from its precursor angiotensin I (a chymases), activate transforming growth factor-h and endothelin (41), but may also lead to decreased levels of angiotensin II (h chymases; ref. 42); and release of tryptase, the major serine protease in mast cells that activates proteinaseactivated receptor 2 on other cell types to induce proliferation and collagen production (43)(44)(45).…”

Spontaneous histamine secretion during isolation of rat cardiac mast cells

“…Thus far our understanding of the mechanisms underlying the function of cardiac mast cells in cardiovascular disease is superficial. However, an association has been established between the increase in mast cell density following ventricular volume overload and the in vivo activation of enzymes that contribute to the adverse remodeling of the extracellular matrix, as well as to the ventricular dilatation associated with heart failure [22][23][24][25][26][27][28]. The isolation of mast cells is necessary for cell specific biochemical, histochemical, or immunological characterization.…”