Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair.
OBJECTIVE
We sought to evaluate: 1) the contribution of dendritic cells (DCs); and 2) the impact of B-cell lymphoma 2 protein (Bcl-2), a central anti-apoptotic protooncogene, and of heat shock protein 47 (HSP47), indicating subsequent collagen deposition, in neointima formation after angioplasty.


BACKGROUND
The origin of neointimal cells and the factors that promote their accumulation are still unclear. Previous studies reported intimal presence of DCs and suggested cells of primarily extravascular origin to contribute to arterial repair.


METHODS
Sprague-Dawley rats underwent carotid balloon angioplasty. At different times after angioplasty, tissue sections were analyzed by immunohistochemistry using OX-62 and S100 as DC markers and antibodies against Bcl-2 and HSP47, supplemented by electron microscopic analysis of cell type and apoptosis.


RESULTS
Four days after injury, DCs adhered along the internal elastic lamina and demonstrated intense Bcl-2 and HSP47 expression, consistent with low apoptosis. With ongoing neointima enlargement, luminal DCs remained prevalent and were colocalized with Bcl-2 and HSP47, while signaling decreased to basal regions. Media showed no DCs and only low Bcl-2 and HSP47 immunoreactivity. Adventitia transiently revealed a structural separation between day 4 and 7. Whereas the inner layer demonstrated sparse cellularity, apoptosis and no DC, Bcl-2, and HSP47 labeling, the outer layer was characterized by high myofibroblast density with strong Bcl-2 and HSP47 expression but absence of DCs.


CONCLUSIONS
We identify DCs as novel components in early neointima formation, promoted by coordinated anti-apoptotic Bcl-2 and HSP47 expression. Despite intense adventitial remodeling, there is no evidence of adventitial cell transmigration.
Bauriedel
Gerhard
G
Department of Medicine-Cardiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Gerhard.Bauriedel@ukb.uni-bonn.de
Jabs
Alexander
A
Skowasch
Dirk
D
Hutter
Randolph
R
Badimon
Juan J
JJ
Fuster
Valentin
V
Welsch
Ulrich
U
Lüderitz
Berndt
B
D000800:Angioplasty, Balloon / Q000009:adverse effects* / Q000295:instrumentation; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020212:Carotid Artery Injuries / Q000209:etiology* / Q000473:pathology*; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000032:analysis / Q000502:physiology / Q000648:ultrastructure; D003713:Dendritic Cells / Q000502:physiology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015607:Stents / Q000009:adverse effects; D013997:Time Factors; D017539:Tunica Intima / Q000737:chemistry / Q000254:growth & development* / Q000293:injuries* / Q000648:ultrastructure; D017540:Tunica Media / Q000254:growth & development; D014945:Wound Healing / Q000502:physiology*
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C494662:Serpinh1 protein, rat; D003094:Collagen