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. 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. 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.
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. 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. 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.
Authors: Michal Pazdernik; Helena Bedanova; Zhi Chen; Josef Kautzner; Vojtech Melenovsky; Ivan Malek; Antonij Slavcev; Michaela Bartonova; Vladimir Karmazin; Tomas Eckhardt; Ales Tomasek; Eva Ozabalova; Tomas Kovarnik; Peter Wohlfahrt; Milan Sonka Journal: Transpl Immunol Date: 2020-10-15 Impact factor: 2.032
Authors: Katrin Splith; Peter Fellmer; Ivan Matia; Martin Varga; Martin Oliverius; Stephanie Kuhn; Linda Feldbrügge; Felix Krenzien; Hans-Michael Hau; Georg Wiltberger; Moritz Schmelzle; Sven Jonas Journal: PLoS One Date: 2014-03-11 Impact factor: 3.240
Authors: Jan Hruby; Rudolf Spunda; Pavel Mericka; Mikulas Mlcek; Ondrej Pecha; Katrin Splith; Moritz Schmelzle; Felix Krenzien; Jaroslav Lindner; Miroslav Spacek; Ivan Matia Journal: PLoS One Date: 2020-03-10 Impact factor: 3.240