Topography of cell replication in human vein graft stenoses

Background - Analysis of the cellular composition of human autogenous vein graft lesions at the time of revision provides an opportunity to identify the cellular processes leading to the development of stenosis in humans after vascular reconstruction. Methods and Results - Human vein graft- threatening stenotic lesions were identified by duplex scanning within 3 to 18 months after infrainguinal bypass and surgically removed. They were serially studied by immunocytochemistry for expression of the proliferating cell nuclear antigen (PCNA) in different cell types: α-actin-positive smooth muscle cells (SMCs), endothelial cells (ECs), monocytes, and macrophages. Proliferation indexes were separately obtained for each layer of the vessel wall by determining the mean percentage of PCNA-positive nuclei among the total number of nuclei present within the intima, the media, and the adventitia, respectively. The percentage distribution of the replicating cell types was also determined. We report that in autogenous vein grafts (n=14) the intima of the lesion displayed fewer PCNA+nuclei (1.03±0.88) than the underlying media (3.14±0.74) or the adventitia (3.01±0.74). Replicating SMCs were predominantly in the medial layer (68% of PCNA + cells) of stenotic vein grafts. In the adventitia, the proliferation was most intense in the endothelium of microvessels (65% of PCNA+nuclei). Conclusions - Our findings reveal a 3-fold greater proliferative activity in the media and the adventitia as compared with the intima of autogenous vein graft lesions, in contrast to cellular proliferation identified in recurrent coronary stenotic plaques. Moreover, there are distinctive patterns of distribution of the different cell populations among the 3 layers. The results indicate a proliferative response of the media and the adventitia of autogenous vein grafts transplanted into the arterial circulation, in addition to the cellular proliferation observed in the intima of the lesion.