Restenosis post angioplasty remains the major limitation of several therapeutic interventions including stent implantation. This explains the ongoing interest in its basic pathogenic mechanisms and factors. The aim of the present study was to assess the localization and maximal expression of Bcl-2, a central antiapoptotic protooncogene, and of heat shock protein 47 (HSP47), a marker of early collagen synthesis, in the context with hyperplastic neointima formation as well as concomitant transmural remodeling processes following angioplasty. 0, 4, 24 and 48 hours, 4, 7 and 14 days post balloon traumatization by use of a rat carotid artery model, specific vascular wall compartments were evaluated concerning area, cell density as well as Bcl-2 and HSP47 expression by immunohistochemistry and morphometry, supplemented by electron microscopy (TEM). Neointimal cell accumulation was detected 4 days post angioplasty, characterized by luminal cells adherent to the internal elastic lamina, associated with maximal Bcl-2 and HSP47 expression amounting to 49% and 41%, respectively. With ongoing neointimal formation, a luminal prevalence of both key determinants and a decreasing expression in basal neointimal areas were found. In the media, a temporally reduced cell density was observed significant at 48 hours post trauma. Constitutive HSP47 expression of the media was constant during the entire observation period, whereas sparse Bcl-2 signalling was induced post angioplasty maximal on day 2 with 3% and on day 14 with 5%. The adventitia demonstrated a transient structural separation between day 4 and 7, exhibiting an inner layer with sparse cellularity and an outer layer with extremely high cell density as well as pronounced neovascularization. In this outer adventitia layer, a high frequency of signals for both Bcl-2 and HSP47 were observed amounting to 29% and 57%, respectively. Complementary TEM analysis gave no evidence of transmural migratory events propagated by adventitial cells and thereby supports early neointimal formation by luminal cell recruitment and marked co-expression of anti-apoptotic Bcl-2 and matrix-generating HSP47 as important survival factors. Clinical implications of these findings may be seen in the integration of proapoptotic substances with temporal efficacy in order to prevent restenosis, e.g., by use of coated stents.
