Antithrombotic Effects of Endocardial Endothelial Cells-Comparison with Coronary Artery Endothelial Cells

The purpose of this study was to assess the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after a brief incubation with cultured EECs. EECs were isolated from the right ventricles of porcine hearts and coronary artery endothelial cells (C-ECs) were also isolated from the same animals. After brief incubations (2-min) of platelet suspensions with cultured EEC and C-EC monolayers, platelet aggregation in response to thrombin and 6-keto-PGF_1α (a stable metabolite of PGI₂) content of platelet suspensions were measured. Platelet aggregation was significantly inhibited by a brief incubation of platelet suspensions with EEC and C-ECs monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 × 10⁻⁵ M) restored platelet activity, but pretreatment with N^ω-nitro-L-arginine methyl ester (L-NAME; 5 × 10⁻⁵ M) or hemoglobin (1 × 10⁻⁶ M) did not. Platelet/EEC interactions multiplicatively increased the 6-keto-PGF_1α content of platelet suspensions and the 6-keto-PGF_1α content of platelet suspensions after incubations with EECs correlated significantly with the inhibition of platelet aggregation. Both the anti-aggregation properties and 6-keto-PGF_1α production were significantly greater in EECs than in C-ECs. A brief incubation (2-min) with PDGF (10 ng/ml) or TGF-β (1 and 10 ng/ml) stimulated 6-keto-PGF_1α production in EECs but not in C-ECs, although these growth factors stimulated 6-keto-PGF_1α production in C-ECs after a longer incubation time (30 or 60 min). In this study, after a brief incubation (2-min) with platelet suspensions, EECs inhibited platelet aggregation mainly through the release of PGI₂ but not EDRF. As this anti-aggregation property was significantly greater in EECs than in C-ECs, it is suggested that endocardial endothelial PGI₂ may inhibit both intracardiac and intracoronary artery thrombus formation, contributing to the prevention of myocardial ischemia.