Retinoic acid inhibition of cardiac mesenchyme formation in vitro correlates with changes in the secretion of particulate matrix from the myocardium

Retinoic acid has been associated with a variety of cardiac defects. A perc entage of these defects are related to changes in the endocardial cushions; Studies in mice and older chick embryos have shown a decrease in mesenchym al cell formation attributable to retinoic acid and have suggested that ret inoic acid was affecting the extracellular matrix. In this study we have te sted the effect of retinoic acid on cardiac mesenchyme formation in vitro a nd then tested retinoic acid treated myocyte cultures for changes in the ex pression of hLAMP-1, fibronectin and transferrin members of the particulate matrix that is required for mesenchyme formation. Initial experiments test ed the effect of retinoic acid on mesenchymal cell formation first in atrio ventricular canal and outflow tract explant cultures and then in AV endothe lial monolayer cultures using myocyte conditioned media or the particulate matrix fraction from retinoic acid treated myocyte cultures.. In all cases, mesenchymal cell formation was suppressed while no suppression was observe d when MyoCM was included with retinoic acid. Protein analysis showed that retinoic acid had a stimulatory effect on protein synthesis. ELISA assays r evealed that retinoic acid treated myocyte, Cultures contained significantl y more hLAMP-1 and fibronectin than either normal or DMSO controls. However , transferrin was not affected by retinoic acid treatment in these experime nts. Our results suggest that retinoic acid affects the expression of the p articulate matrix and that these changes may be responsible for the observe d decrease in mesenchymal cell formal;ion. Anat Rec 258:186-197, 2000. (C) 2000 Wiley-Liss, Inc.