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Direct and indirect effects of alloantibodies link neointimal and medial remodeling in graft arteriosclerosis.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2006 Oct; Vol. 26 (10), pp. 2359-65. Date of Electronic Publication: 2006 Aug 17. - Publication Year :
- 2006
-
Abstract
- Objective: Chronic vascular rejection, the main cause of allograft failure, is characterized by the destruction of smooth muscle cells (SMCs) in the media concomitantly with the proliferation of SMCs in the adjacent neointima. We hypothesized that alloantibodies might be responsible for these 2 opposite but coordinated events.<br />Methods and Results: We used the rat aortic interposition model of chronic vascular rejection. During the rejection process, a neointima composed of proliferating SMCs from the recipient developed, whereas the SMCs in the media, all of donor origin, underwent apoptosis. Alloantibody deposition was detected only in the media. Using in vitro cultures experiments, we observed that alloantibody binding to donor SMCs exerts (1) a rapid upregulation of the transcription of growth factors genes, followed by (2) the induction of apoptosis after 24 hours. The transient production of growth factors by donor SMCs in response to the binding of alloantibodies induced the proliferation of recipient SMCs in culture supernatant transfer experiments. Additional data suggest that among the repertoire of alloantibodies, those directed against major histocompatibility complex I might carry the remodeling effect.<br />Conclusions: Our data suggest that during chronic vascular rejection, alloantibody binding to donor medial SMCs is a crucial event that links neointimal and medial remodeling.
- Subjects :
- Animals
Aorta immunology
Aorta physiopathology
Arteriosclerosis immunology
Cell Proliferation drug effects
Cell Survival
Cells, Cultured
Chronic Disease
Culture Media, Conditioned pharmacology
Graft Occlusion, Vascular immunology
Graft Rejection immunology
Graft Rejection pathology
Growth Substances genetics
Isoantibodies biosynthesis
Isoantibodies pharmacology
Kinetics
Major Histocompatibility Complex immunology
Male
Myocytes, Smooth Muscle pathology
Rats
Rats, Inbred BN
Rats, Inbred Lew
Tissue Donors
Transcription, Genetic
Transplantation Chimera
Tunica Intima immunology
Tunica Media immunology
Up-Regulation drug effects
Arteriosclerosis physiopathology
Graft Occlusion, Vascular physiopathology
Graft Rejection physiopathology
Isoantibodies immunology
Tunica Intima physiopathology
Tunica Media physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 26
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16917106
- Full Text :
- https://doi.org/10.1161/01.ATV.0000241980.09816.ac