Expression rate of vinculin isoforms in human aortocoronary saphenous vein grafts

Abstract

Aortocoronary bypass conduits derived from saphenous veins usually develop diffuse intimal thickening, one of the major causes of haemodynamically relevant graft stenosis. To elucidate the role of smooth muscle cell proliferation in late graft failure, specimens from highly stenotic or occluded vein grafts implanted into the arterial circulation for more than 5 years were tested for their expression rate of meta-vinculin. Since the cytoskeletal protein meta-vinculin is present exclusively in contractile smooth muscle cells, the determination of the relative amounts of meta-vinculin (150 kDa) and its low-molecular weight isoform vinculin (130 kDa) allows characterization of the phenotypic status of smooth muscle cells. Using immunoblotting techniques, the quantitative relation of meta-vinculin in tissue samples obtained from autoptic vein grafts ( n=10) was measured and compared with those of native saphenous veins ( n=6). In vein grafts, the fractional meta-vinculin content of the total vinculin immunoreactivity ranged from 32%–46% (mean 39.6%), whereas the range was 39%–53% (mean 46.7%) in native veins. By applying Student's t-test, a statistical significance was not demonstrated suggesting that the majority of smooth muscle cells in intimal thickenings consisted of a contractile phenotype. Immunohistochemically, the vinculin immunoreactivity in the intimal layer of vein grafts was reduced as compared to native saphenous veins. The distribution of vinculin in grafted veins closely resembled that in arteriosclerotic coronary arteries with intimal thickening. Hence, our biochemical data demonstrate parallels between the pathogenesis of late vein graft stenosis and degenerative arteriosclerotic lesions.