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.


METHODS
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 actin-positive (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.


CONCLUSIONS
At late follow-up, the majority of intimal cells are smoothelin-positive indicating that adventitial myofibroblasts play no major role for neointima formation.
Maeng
Michael
M
Department of Cardiology, Aalborg Hospital, Denmark. michael.maeng@iekf.au.dk
Mertz
Henrik
H
Nielsen
Søren
S
van Eys
Guillaume J J M
GJ
Rasmussen
Klaus
K
Espersen
Geert T
GT
D000199:Actins / Q000032:analysis; D000800:Angioplasty, Balloon; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology*; D019394:Ki-67 Antigen / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D009130:Muscle, Smooth / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors; D017539:Tunica Intima / Q000166:cytology* / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D009124:Muscle Proteins; D003094:Collagen