Transplant vasculopathy: a model for coronary artery disease?
Although transplant vasculopathy and native atherosclerosis are clinically and pathologically different entities, the pathogenesis of both diseases exhibits some common mechanisms. Both may be regarded as responses to injury within a broadened concept of the immune system. Alloantigens (e.g. on donor endothelial cells) or autoantigens (e.g. oxydized LDL cholesterol) 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. Monocyte-derived macrophages are also involved in this process which culminates in rolling, sticking, and diapedesis through the coronary vascular endothelium and phenotype switch of medial smooth muscle cells mediated by generation of growth-promoting cytokines. Thus, viewed within a broadened paradigm of the immune system's role both disease entities may represent different vignettes of an integrated pathophysiological response to an endothelial injury.
Deng
M C
MC
Department of Cardiothoracic Surgery, Muenster University Hospital. deng@uni-muenster.de
Plenz
G
G
Erren
M
M
Wilhelm
M J
MJ
Moennig
G
G
Rothenburger
M
M
Baba
H A
HA
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002908:Chronic Disease; D003327:Coronary Disease / Q000209:etiology / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D015854:Up-Regulation
D001324:Autoantigens; D016207:Cytokines; D007519:Isoantigens; D019001:Nitric Oxide Synthase