Mechanismen der Transplantatvaskulopathie

Zusammenfassung

Die Transplantatvaskulopathie des Spenderherzens ist eine diffuse, obliterative Form der Arteriosklerose, charakterisiert durch die Produktion einer Neointima reich an glatten Muskelzellen, die langfristig zu einer Obstruktion des Lumens führt. Pathophysiologisch werden nach Herztransplantation Alloantigene (z. B. auf Spender-Endothelzellen) durch antigen-präsentierende Zellen den T-Zellen des körpereigenen Immunsystemes präsentiert. Mit dem geeigneten kostimulatorischen Signal erzeugt dieses Muster eine differenzierte T-Zell-, B-Zell-Antwort und eine inflammatorische Antwort, während es ohne dieses Zweitsignal zur Apoptose der Immunzellen kommt. Im Falle einer Proliferation und Differenzierung der Immunzellen wird ein koordiniertes Zytokin-Muster initiiert. In diesen Prozess einbezogen sind Zellen der angeborenen Immunabwehr, von Monozyten abstammende Makrophagen. Die Zytokinfreisetzung führt zum Rolling, Sticking und der Diapedese von Immunzellen durch die koronare Endothelschicht und zu Migration der Media-ständigen glatten Muskelzellen und einem Wechsel ihres Phänotyps mit Produktion von wachstumsfördernden Zytokinen, die zur Intimahyperplasie beitragen.

Summary

Cardiac allograft vasculopathy is a diffuse, obliterative form of arteriosclerosis that is characterized by the production of a neointima rich in vascular smooth muscle cells that progressively obstructs the lumen. Pathophysiologically, after heart transplantation, alloantigens (e. g. on donor endothelial cells) are presented by antigen presenting cells to the T-cells of the body’s immune system. With the appropriate costimulatory signal, this signal pattern generates a differentiated T-cell, B-cell, and inflammatory cell response whereas without the second signal, the immune cells undergo apoptosis. In case of immune cell proliferation and differentiation, a coordinated pattern of cytokine release is initiated. Cells of innate immunity, monocyte-derived macrophages, are involved in this process. The inflammatory response culminates in rolling, sticking, and diapedesis through the coronary vascular endothelium and migration and phenotype switch of medial smooth muscle cells mediated by generation of growth-promoting cytokines.

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