Adventitial myofibroblasts play no major role in neointima formation after angioplasty

Objective-Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts. Design-Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for alpha-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype). Results-Adventitial cells became transiently actinpositive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82+/-10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen. Conclusion-At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.