Increased interleukin-1 beta and fibronectin expression are early features of the development of the postcardiac transplant coronary arteriopathy in piglets.
The mechanism causing intimal thickening in the postcardiac transplant coronary arteriopathy (PCTCA) is associated with interactions between inflammatory cells and vascular cells. Our previous studies related intimal thickening to fibronectin-dependent smooth muscle cell (SMC) migration into the subendothelium, and others have shown that cytokines, eg, interleukin (IL)-1 beta, up-regulate SMC fibronectin synthesis. In this study, we identified, in piglets, features compatible with early development of the PCTCA. Ultrastructure revealed increased SMC and inflammatory cells in the subendothelium. Immunohistochemistry showed major histocompatibility complex II presentation in the endothelium and adventitia, associated with infiltration of different subsets of inflammatory cells; increased IL-1 beta, particularly in the endothelium; and fibronectin, in the subendothelium and inner media, the latter confirmed by quantitative immunoelectron microscopy. In the PCTCA, increases in IL-1 beta and fibronectin could mediate adherence, transendothelial migration and trapping of inflammatory cells, and SMC migration into the subendothelium.
Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Ontario, Canada.
N
N
Clausell
S
S
Molossi
M
M
Rabinovitch
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005353:Fibronectins / Q000032:analysis* / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism* / Q000502:physiology*; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D013552:Swine / Q000378:metabolism*
D005353:Fibronectins; D007375:Interleukin-1