INCREASE AND REDISTRIBUTION OF CARDIAC MAST-CELLS IN AURICULAR THROMBOSIS - POSSIBLE ROLE OF KIT-LIGAND

Background The atrial appendage is a predilection site for thrombus fo rmation. Mast cells (MC) are a rich source of mediators that may be in volved in the regulation of thrombus formation. We examined number, di stribution, and phenotype of MC in thrombosed versus unaffected auricl es to elucidate their possible role in auricular thrombosis (AUTHR). M ethods and Results Sections of atrial appendages(AUTHR, n=14; controls (CO), n=13) were analyzed for MC by Giemsa, toluidine blue, and berbe rine sulfate stains and by immunohistochemistry. Cardiac MC expressed CD antigens corresponding to the classic MC phenotype as well as trypt ase, chymase, and heparin. Thrombosis was associated with a twofold in crease in the number of MC in the total appendage (CO, 3.1+/-1.0 versu s AUTHR, 6.4+/-1.1 MC/mm(2), P<.01). Moreover, in AUTHR, a redistribut ion of MC to the upper endocardium was observed (AUTHR, 5.3+/-1.4 vers us CO, 0.07+/-0.15 MC/mm(2), P<.01). Mast cell growth factor (MGF) was expressed in the endothelium and subendothelial space of thrombosed a ppendages but not in the normal endocardium. Overexpression of MGF was accompanied by a weak or absent expression of the MGF receptor c-kit on redistributed MC in AUTHR. Patients with unilateral atrial appendag e thrombosis did not exhibit a MC increase or redistribution in the un affected contralateral appendage. No augmentation of other inflammator y cells was observed. Stimulation of isolated cardiac MC with MGF resu lted in mediator release. Conclusions This study provides evidence tha t AUTHR is associated with MC increase and redistribution and MGF over expression. The role of redistributed MC and their mediators in the pa thophysiology of atrial thrombosis requires further investigation.