Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis

Abstract Background and aims Neointimal cellular proliferation of fibroblasts and myofibroblasts is documented in coronary artery restenosis, however, their role in peripheral arterial disease (PAD) restenosis remains unclear. Our aim was to investigate the role of fibroblasts, myofibroblasts, and collagens in restenotic PAD. Methods Nineteen PAD restenotic plaques were compared with 13 de novo plaques. Stellate cells (HE p  = 0.04) and apoptosis (14.6% ± 1.3 vs. 11.2% ± 0.6; p  = 0.03) were increased in restenotic plaques. Finally, SMMHC (2.6 ± 0.12 vs. 1.4 ± 0.15; p  = 0.0001), type III collagen density (0.33 ± 0.06 vs. 0.17 ± 0.07; p  = 0.0001), IL-6 (2.08 ± 1.7 vs. 1.03 ± 2.0; p  = 0.01), and TGF-β (1.80 ± 0.27 vs. 1.11 ± 0.18; p  = 0.05) were increased in restenotic plaques. Conclusions Our study suggests proliferation and apoptosis of fibroblast and myofibroblast with associated increase in type III collagen may play a role in restenotic plaque progression. Understanding pathways involved in proliferation and apoptosis in neointimal cells, may contribute to future therapeutic interventions for the prevention of restenosis in PAD.