Accelerated atheromatous lesions in mouse hearts transplanted to apolipoprotein-E-deficient recipients.
Arteriopathy, sometimes termed accelerated atherosclerosis, often impairs transplants. We employed apolipoprotein-E-deficient, hypercholesterolemic mice to determine how the hyperlipidemic environment affected transplanted hearts. Strain 129 hearts transplanted to C57BL/6 normal or C57BL/6 apolipoprotein-E-deficient recipients were evaluated by immunochemical and histological techniques. Analyses were possible both of differences in the coronary lesions that developed in a normolipidemic as compared with a hyperlipidemic environment and of the coronary atherosclerotic process in transplanted hearts compared with native hearts in the same hyperlipidemic environment. Aortas and coronary arteries of transplanted aortas in both recipient groups developed florid intimal thickening by 4 to 10 weeks, with marked lipid deposition, foamy macrophages, and infiltration of smooth muscle alpha-actin-positive cells in apolipoprotein-E-deficient mice. Lipid was layered against the internal elastic lamina as in human transplants. VCAM-1 was increased in various sites in both groups. Allotransplants to apolipoprotein-E-deficient recipients had more severe aortic and coronary lesions with characteristic T cell infiltration than native hearts. In this sense, transplants suffered from accelerated atherosclerosis. The character of coronary vascular changes in transplanted hearts was distinctly affected by their lipid environment, but their severity, in terms of luminal encroachment, was not markedly different.
Russell
P S
PS
Transplantation Unit of the Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
Chase
C M
CM
Colvin
R B
RB
D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000737:chemistry / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D016027:Heart Transplantation / Q000473:pathology*; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D001057:Apolipoproteins E; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1