Antithrombin III Inhibits Mesangial Cell

Thrombin stimulates and heparin and heparan sulfate inhibit mesangial cell proliferation. In addition, heparin has been shown to inhibit thrombin-stimulated smooth muscle cell proliferation. The anticoagulant action of heparin is mediated by antithrombin Ill. This study investigated whether heparin’s antiproliferative action is also mediated by antithrombin Ill. To this end, the effect of antithrombin Ill on thrombinstimulated mesangial cell growth was examined. As expected, thrombin stimulated DNA synthesis and cell growth in cultured human mesangial cells. The effect of thrombin on DNA synthesis and mesangial cell proliferation was inhibited by standard heparin and antithrombin Ill, separately or together. The magnitude of the inhibitory action of antithrombin Ill was equal to that of equimolar concentrations of heparin and that observed with the combination of the two. Experiments carried out in serum (hence antithrombin 111)-free medium revealed that heparin’s inhibitory effects are independent of antifhrombin Ill. It was concluded that antithrombin Ill, an endogenous inhibitor of thrombin’s coagulant activity, is an equally effective inhibitor of thrombin’s mitogenic action.