IMMUNOHISTOCHEMICAL DEMONSTRATION OF 15-LIPOXYGENASE IN TRANSPLANT CORONARY-ARTERY DISEASE

15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic and l inoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). 15-LO mRNA and protein have previousl y been demonstrated in macrophages of rabbit and human atherosclerotic lesions. The purpose of this study was to investigate whether 15-LO i s also present in the accelerated form of coronary artery disease that can complicate cardiac transplantation (TCAD). Immunohistochemical an alysis of coronary arteries with TCAD was carried out by using a rabbi t polyclonal antibody raised against human recombinant 15-LO and an av idin-biotin-immunoperoxidase system. Normal coronary and pulmonary art eries 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 immunore activity for 15-LO was present in these lesions. The second type of gr aft arteriosclerosis consisted of complex atheromatous lesions, contai ning myointimal cells, lipid-laden foam cells, fragmented internal ela stic laminae, and calcifications. 15-LO immunostaining of myointimal c ells, lipid-laden foam cells, and endothelial cells was consistently p resent in these atheromatous lesions. The majority of the myointimal a nd foam cells positive for 15-LO were recognized by antisera to alpha- smooth muscle actin; the others were identified as macrophages. The re sults indicate that 15-LO expression is present in endothelial, myoint imal, and foam cells in complex atheromatous lesions of TCAD, and sugg est that 15-LO may play a role in the pathogenesis of this form of the disease.