Immediate-early gene expression in human saphenous veins harvested during coronary artery bypass graft operations

Saphenous vein graft occlusion is a common late complication of coronary bypass grafting. Intimal smooth muscle cell hyperplasia is a component of this pathobiology, but the underlying molecular events are poorly understood. Immediate-early genes are activated shortly after growth stimulation and subserve cellular functions, which may contribute to intimal smooth muscle cell accumulation. In the present study, human saphenous vein grafts were harvested with minimal manipulation during coronary bypass and processed for isolation of total ribonucleic acid to examine changes in immediate-early gene expression of messenger ribonucleic acid by Northern blotting techniques. Thirty saphenous vein grafts were incubated at 4° C in Dulbecco's modified Eagle media from 30 minutes to 10 hours. The messenger ribonucleic acids for immediate-early genes c-fos and c-myc were weak or undetectable in controls but were increased (>10 times controls) within 1 hour (c-fos) and persisted for at least 6 hours (c-myc) after harvest. Our results demonstrate, for the first time in human vascular tissue, incipient immediate-early gene induction. This information may lead to molecular therapies to control saphenous vein graft disease

The Effect of Thrombocytopenia on Experimental Arteriosclerotic Lesion Formation in Rabbits SMOOTH MUSCLE CELL PROLIFERATION AND RE-ENDOTHELIALIZATION

the mechanisms involved in fibromusculoelastic lesion formation produced by selective de-endothelialization by the intra-arterial balloon catheter technique in thrombocytopenic rabbits. Thrombocytopenia was induced and maintained for up to 31 days by daily injections of highly specific sheep anti-rabbit platelet sera (APS). Evidence for re-endothelialization was obtained by i.v. Evans blue dye 30 min before sacrifice. Rabbits received daily injections of APS, which reduced the mean platelet count to 5,600/cm3; control animals received identically treated normal sheep sera on the same schedule, and had mean daily platelet counts of 363,000/cm3. Evaluation of intimal thickness was assessed by counting cell layers in semithin sections. Intimal thickening in aortae from rabbits treated with APS was strikingly suppressed, in contrast to those from normal sheep sera-treated animals which showed a mean intimal thickness of 18 cell layers within 28 days often after de-endothelialization. Re-endothelialization was not affected by APS treatment. These results indicate that the proliferation of smooth muscle cells which is characteristic of arteriosclerotic lesions is dramatically inhibited by reduction of platelets. Dr. Stemerman is currently Head ofThrombosis and Hemostasi