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.
Lefer
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Tsao
P S
PS
Ma
X L
XL
Sampath
T K
TK
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects; D010477:Perfusion; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011506:Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta