SPID#: 38 These studies are designed to evaluate mechanisms and strategies for the prevention of vascular lesion formation induced by arterial injury. Restenosis that develops after interventional procedures for symptomatic atherosclerotic disease (e.g. balloon catheter angioplasty) frequently compromises the benefits of treatment. The present experiments were designed to test the role of the platelet-derived growth factor (PDGF) in the restenotic process. PDGF was originally identified as a releasable component of platelet granules, but has now been identified in other vascular cells including macrophages and endothelial cells and is thought to play a key role in orchestrating the vascular response to injury. This hypothesis was tested by by infusion of a monoclonal antibody (2A1E2) against the platelet-derived growth factor (-receptor (PDGF-R). This antibody recognizes only human and baboon PDGF-R. Therefore, baboons were evaluated following single daily bolus injections of the antibody, which produced plasma levels ranging between 150 and 100 nM (peak-to-trough levels). Although the antibody was only administered for the first 7 days after balloon catheter injury of the superficial femoral artery (similar in size to human coronary arteries) the extent of arterial wall thickening at 30 days was strikingly reduced by 40-45%. This study demonstrates that 1) the PDGF pathway is important for arterial injury repair in primates; 2) early short-term blockade of this pathway may produce a late anti-restenotic benefit after discontinuance of therapy; and 3) the monoclonal antibody 2A1E2 may be an attractive therapeutic agent for anti-arteriosclerotic applications in man.
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