European Heart Journal Advance Access originally published online on November 2, 2005
European Heart Journal 2006 27(1):116; doi:10.1093/eurheartj/ehi632
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Role of dendritic cells in specific atherosclerosis types
Department of Internal Medicine II/Cardiology
University of Bonn
Sigmund-Freud-Str. 25
D-53127 Bonn
Germany
Tel: +49 228 287 6670
Fax: +49 228 287 4983
E-mail address:
gerhard.bauriedel{at}ukb.uni-bonn.de
Department of Internal Medicine II/Cardiology
University of Bonn
Germany
Institute of Anatomy II
University of Munich
Germany
Department of Internal Medicine II/Cardiology
University of Bonn
Germany
We have read with great interest the recent article on dendritic cells (DCs) in atherosclerosis by Bobryshev1 that reviewed the current status of the problem and its clinical relevance. We believe that the author correctly pointed out the role of DCs in the non-diseased vascular wall and in pre- atherosclerotic stages. In addition, he gave a brilliant summary of recent DC findings in manifest vascular lesions, predominantly based on animal work, mainly resulting from the lack of systematically analysed human plaque tissue. However, the author failed to acknowledge that DCs were also found in symptomatic human in-stent restenosis (ISR)2 as well as in neointima formation after rat carotid balloon injury.3 First, the latter longitudinal animal data demonstrated DCs adhering along the internal elastic lamina and forming incipient neointima, strongly colocalized with intense Bcl-2 and HSP47 expression as determinants of cell survival and subsequent matrix formation. These and other findings4 strengthen the concept of co-ordinated anti-apoptotic signals specifically bound to DCs that preserve cellular integrity until neointimal tissue consolidation occurs, thereby promoting neointima formation.3 Secondly, we showed that the frequency of DCs in tissue probes retrieved from patients with clinical ISR was seven-fold higher when compared with that found in probes from de novo lesions. In addition, the same ISR probes were characterized by low frequency of pathogen burden, inflammation and apoptosis, and absence of proliferation.5
Therefore, beyond acknowledging the presence of DCs in hypercellular neointima, we would like to state that it is still too early to develop the conclusion that DCs promote plaque destabilization.1 We feel that the mere presence of these cells in plaque regions prone to rupture does not exclusively imply that DCs contribute to impaired plaque integrity, but also suggests that these cells are involved in (neo)intimal repair processes.
With respect to DCs and therapeutic intervention in atherosclerosis, in particular, DCs that are implicated in early neointima formation and that exclusively populated the neointimal site3 seem attractive as carriers for targeted therapies such as DC-mediated gene transfer or other modalities. Of note, recent work of our group revealed neointimal DCs to represent the predominant cell type exhibiting FKBP-12 binding sites for rapamycin early post-vascular injury.6 Therefore, we propose that the marked prevention of restenosis by use of sirolimus-eluting stents, as widely shown, is primarily mediated by effects on neointimal DCs. Likewise, rapamycin specifically induced apoptosis in monocyte and CD34-derived DCs but not in monocytes and macrophages.7
References
- Bobryshev YV. Dendritic cells in atherosclerosis: current status of the problem and clinical relevance. Eur Heart J 2005;26:1700–1704.
[Abstract/Free Full Text] - Skowasch D, Jabs A, Andrié R, Dinkelbach S, Lüderitz B, Bauriedel G. Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis. Cardiovasc Res 2003;60:684–691.
[Abstract/Free Full Text] - Bauriedel G, Jabs A, Skowasch D, Hutter R, Badimon JJ, Fuster V, Welsch U, Lüderitz B. Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression with anti-apoptotic Bcl-2 and HSP47 in arterial repair. J Am Coll Cardiol 2003;42:930–938.
[Abstract/Free Full Text] - Pollman MJ, Hall JL, Mann MJ, Zhang L, Gibbons GH. Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat Med 1998;4:222–227.[CrossRef][ISI][Medline]
- Skowasch D, Jabs A, Andrié R, Dinkelbach S, Schiele TM, Wernert N, Lüderitz B, Bauriedel G. Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis. J Vasc Res 2004;41:525–534.[CrossRef][ISI][Medline]
- Bauriedel G, Jabs A, Krämer S, Yeghiazaryan K, Lüderitz B. Rapamycin receptor FKBP12 in neointimal dendritic cells post angioplasty. Eur Heart J 2003;24(Suppl.):434.
- Woltman AM, de Fijter JW, Kamerling SWA, van Der Kooij SW, Paul LC, Daha MR, van Kooten C. Rapamycin induces apoptosis in monocyte- and CD34-derived dendritic cells but not in monocytes and macrophages. Blood 2001;98:174–180.
[Abstract/Free Full Text]
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