Immunohistochemical demonstration of 15-lipoxygenase in transplant coronary artery disease.
15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic and linoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). 15-LO mRNA and protein have previously been demonstrated in macrophages of rabbit and human atherosclerotic lesions. The purpose of this study was to investigate whether 15-LO is also present in the accelerated form of coronary artery disease that can complicate cardiac transplantation (TCAD). Immunohistochemical analysis of coronary arteries with TCAD was carried out by using a rabbit polyclonal antibody raised against human recombinant 15-LO and an avidin-biotin-immunoperoxidase system. Normal coronary and pulmonary arteries showed no immunostaining for 15-LO. Two different types of TCAD were observed. One type consisted of concentric intimal proliferation of smooth muscle cells, without lipid or calcium deposits. No immunoreactivity for 15-LO was present in these lesions. The second type of graft arteriosclerosis consisted of complex atheromatous lesions, containing myointimal cells, lipid-laden foam cells, fragmented internal elastic laminae, and calcifications. 15-LO immunostaining of myointimal cells, lipid-laden foam cells, and endothelial cells was consistently present in these atheromatous lesions. The majority of the myointimal and foam cells positive for 15-LO were recognized by antisera to alpha-smooth muscle actin; the others were identified as macrophages. The results indicate that 15-LO expression is present in endothelial, myointimal, and foam cells in complex atheromatous lesions of TCAD, and suggest that 15-LO may play a role in the pathogenesis of this form of the disease.
Ravalli
S
S
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Marboe
C C
CC
D'Agati
V D
VD
Michler
R E
RE
Sigal
E
E
Cannon
P J
PJ
D000328:Adult; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011183:Postoperative Complications; D012016:Reference Values
D001093:Arachidonate 15-Lipoxygenase