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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:340-348.)
© 1995 American Heart Association, Inc.

Articles

Immunohistochemical Demonstration of 15-Lipoxygenase in Transplant Coronary Artery Disease

Stefano Ravalli; Charles C. Marboe; Vivette D. D'Agati; Robert E. Michler; Elliott Sigal; Paul J. Cannon

From the Departments of Medicine, Division of Cardiology (S.R., P.J.C.), Cardiothoracic Surgery (R.E.M.), and Pathology (C.C.M., V.D.D.), Columbia University College of Physicians and Surgeons, New York, NY, and Syntex Discovery Research (E.S.), Palo Alto, Calif.

Correspondence to Paul J. Cannon, MD, Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032.

Abstract 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 –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.

Key Words: 15-lipoxygenase • graft arteriosclerosis • transplantation • lipid oxidation • coronary artery disease

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