Endothelial apoptosis and chronic transplant vasculopathy: recent results, novel mechanisms.
Chronic transplant vasculopathy (CTV) is a progressive form of vascular obliteration affecting the arteries, arterioles and capillaries of solid organ transplants. It is characterized by intimal accumulation of mononuclear cells, vascular smooth muscle cells (VSMC), myofibroblasts and connective tissue. Mounting evidence, based on animal models and human biopsy results, suggests that acute and persistent rejection triggering apoptosis of endothelial cells (EC) plays a pivotal role in CTV. The precise mechanisms that underlie the induction of fibroproliferative changes in association with endothelial apoptosis have yet to be clearly delineated. Recent observations in the field of apoptosis research provide some important mechanistic clues. First, endothelial apoptosis creates a state of hyperadhesiveness for mononuclear cells, thus facilitating sustained leukocyte infiltration. Second, phosphatidylserine-dependent engulfment of apoptotic cells by infiltrating mononuclear leukocytes promotes transforming growth factor-beta1 production. Third, apoptosis of EC triggers extracellular matrix (ECM) proteolysis thus initiating the production of fibroproliferative/fibrogenic ECM fragments. The relative importance of these mechanisms in the pathophysiology of CTV will need to be addressed in vivo. Yet, these recent developments provide a new mechanistic framework that will help better define the importance of immune-mediated EC apoptosis in the regulation of vascular repair.
Cailhier
J-F
JF
Renal and Transplantation Division, Research Centre CHUM (Centre Hospitalier de l'Université de Montréal), University of Montreal, 1560 Sherbrooke Est, Montreal, Quebec H2L 4M1, Canada.
Laplante
P
P
Hébert
M-J
MJ
D017209:Apoptosis; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D011183:Postoperative Complications / Q000473:pathology* / Q000503:physiopathology; D014184:Transplantation, Homologous / Q000473:pathology; D014652:Vascular Diseases / Q000473:pathology* / Q000503:physiopathology