Anti-ischaemic and endothelial protective actions of recombinant human osteogenic protein (hOP-1).

Osteogenic protein one (hOP-1), a member of the transforming growth factor-beta (TGF-beta) supergenic family, was studied for its anti-ischaemic properties in rats subjected to myocardial ischaemia and reperfusion. Ten minutes after ligation (i.e., just prior to reperfusion) of the left coronary artery, 2 or 20 micrograms/rat recombinant human (hOP-1) or its vehicle, was given intravenously. hOP-1 at 20 micrograms significantly reduced reperfusion injury 24 h later compared to rats receiving only vehicle (i.e., 0.9% NaCl). hOP-1 was also found to preserve rat coronary endothelial function (i.e., release of endothelium-derived relaxing factor, EDRF) in perfused hearts following global ischaemia and reperfusion. Moreover, hOP-1 also significantly inhibited adherence of rat neutrophils to rat vascular endothelium in vitro. Thus, hOP-1 exerts significant anti-ischaemic effects. Some of this cardioprotection may be related to the ability of hOP-1 to preserve endothelial function and inhibit neutrophil adherence to the endothelium.