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

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15 Scopus citations

Abstract

15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic acid 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 α-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.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1995
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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