Lipoxygenase products increase monocyte adhesion to human aortic endothelial cells

Mary Kim Patricia, Jeong A. Kim, Cynthia M. Harper, Peggy T. Shih, Judith A. Berliner, Rama Natarajan, Jerry L. Nadler, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


The development of atherosclerosis is accelerated in individuals with type 2 diabetes. Adhesion of monocytes to the vascular endothelium is a key initial step in atherogenesis. We have previously shown that monocyte adhesion to human aortic endothelial cells (HAECs) cultured long-term in high-glucose medium (25 mmol/L, 2 passages) is increased compared with cells grown in normal glucose (5 mmol/L). One potential mechanism for increased monocyte adhesion to HAECs under hyperglycemic conditions is via the 12- lipoxygenase (12-LO) pathway. In this study, we demonstrated in HAECs that the major LO metabolite of arachidonic acid was the 12-LO product, 12(S)- hydroxyeicosatetraenoic acid [12(S)-HETE], which was increased severalfold in HAECs cultured under high-glucose conditions. Furthermore, treatment of HAECs with 12(S)-HETE induced monocyte, but not neutrophil, adhesion an average of 3-fold (range of 1.5- to 5-fold) compared with untreated cells (75±5 versus 26±1 monocytes per field, respectively, P<0.001). Expression of the adhesion molecules vascular cell adhesion molecule-1, E-selectin, and intercellular adhesion molecule-1 was not significantly increased. However, both glucose and 12(S)-HETE induced a 60% increase in HAEC surface expression of connecting segment-1 (ie, CS-1) fibronectin, a ligand for very late-acting antigen-4 (VLA-4). The antibodies used to block monocyte integrin VLA-4 and leukocyte function-related antigen-1, a monocytic counterreceptor for intercellular adhesion molecule-1, inhibited the ability of both 12-LO products and high glucose to induce monocyte adhesion. These results definitively demonstrate for the first time in HAECs that the 12-LO pathway can induce monocyte-endothelial cell interaction and that the effects of glucose may be mediated, at least in part, through this pathway. Thus, these results suggest that the 12-LO pathway may play a role in the increased susceptibility of diabetics to atherosclerosis.

Original languageEnglish (US)
Pages (from-to)2615-2622
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number11
StatePublished - 1999
Externally publishedYes


  • 12(S)-hydroxyeicosatetraenoic acid
  • Endothelium
  • Hyperglycemia
  • Lipoxygenase
  • Monocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Lipoxygenase products increase monocyte adhesion to human aortic endothelial cells'. Together they form a unique fingerprint.

Cite this