BASIC RESEARCH
Dendritic cells in neointima formation after rat carotid balloon injury
coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair
Gerhard Bauriedel, MD, FACC*,*,
Alexander Jabs, BS*,
Dirk Skowasch, MD*,
Randolph Hutter, MD ,
Juan J. Badimon, PhD, FACC,
Valentin Fuster, MD, PhD, FACC,
Ulrich Welsch, MD, PhD and
Berndt Lüderitz, MD, FACC*
* Department of Medicine–Cardiology, University of Bonn, Bonn, Germany
The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York, USA
Institute of Anatomy, University of Munich, MunichGermany
Manuscript received June 27, 2002;
revised manuscript received April 9, 2003,
accepted April 24, 2003.
* Reprint requests and correspondence: Dr. Gerhard Bauriedel, Department of Cardiology, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Gerhard.Bauriedel{at}ukb.uni-bonn.de
OBJECTIVES: 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.
|
Abbreviations and Acronyms
| | Bcl-2 | = B-cell lymphoma 2 protein | | CD34 | = hematopoietic stem cell marker | | DC | = dendritic cell | | EC | = endothelial cell | | HSP47 | = heat shock protein 47 | | OX-62 | = dendritic cell marker | | S100 | = dendritic cell marker | | SMC | = smooth muscle cell | | TEM | = transmission electron microscopy |
|
This article has been cited by other articles:
|
|
|
|
 
A. Jabs, S. Gobel, P. Wenzel, A. L. Kleschyov, M. Hortmann, M. Oelze, A. Daiber, and T. Munzel
Sirolimus-induced vascular dysfunction increased mitochondrial and nicotinamide adenosine dinucleotide phosphate oxidase-dependent superoxide production and decreased vascular nitric oxide formation.
J. Am. Coll. Cardiol.,
June 3, 2008;
51(22):
2130 - 2138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Skowasch, G. Nickenig, and G. Bauriedel
Progenitor Cells and Valve Degeneration
Circ. Res.,
May 26, 2006;
98(10):
e71 - e71.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D Skowasch, S Schrempf, C J Preusse, J A Likungu, A Welz, B Luderitz, and G Bauriedel
Tissue resident C reactive protein in degenerative aortic valves: correlation with serum C reactive protein concentrations and modification by statins
Heart,
April 1, 2006;
92(4):
495 - 498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bauriedel, D. Skowasch, U. Welsch, and B. Luderitz
Role of dendritic cells in specific atherosclerosis types
Eur. Heart J.,
January 1, 2006;
27(1):
116 - 116.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. V. Bobryshev
Role of dendritic cells in specific atherosclerosis types: reply
Eur. Heart J.,
January 1, 2006;
27(1):
116 - 117.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Skowasch, S. Schrempf, N. Wernert, M. Steinmetz, A. Jabs, I. Tuleta, U. Welsch, C. J. Preusse, J. A. Likungu, A. Welz, et al.
Cells of primarily extravalvular origin in degenerative aortic valves and bioprostheses
Eur. Heart J.,
December 1, 2005;
26(23):
2576 - 2580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D Skowasch, A Jabs, R Andrie, B Luderitz, and G Bauriedel
Progression of native coronary plaques and in-stent restenosis are associated and predicted by increased pre-procedural C reactive protein
Heart,
April 1, 2005;
91(4):
535 - 536.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bauriedel, D. Skowasch, A. Jabs, S. Kramer, R. Andrie, and B. Luderitz
Circulating monocytes and late in-stent restenosis
J. Am. Coll. Cardiol.,
August 18, 2004;
44(4):
936 - 936.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Fukuda, K. Shimada, A. Tanaka, T. Kawarabayashi, M. Yoshiyama, and J. Yoshikawa
Circulating monocytes and late in-stent restenosis: Reply
J. Am. Coll. Cardiol.,
August 18, 2004;
44(4):
936 - 937.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Skowasch, A. Jabs, B. Luderitz, and G. Bauriedel
Bone Marrow-Derived Cells and Vascular Growth
Circ. Res.,
April 30, 2004;
94(8):
e71 - e71.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel
Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis
Cardiovasc Res,
December 1, 2003;
60(3):
684 - 691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
