Premium
The isoprostane 8‐iso‐PGF 2α stimulates endothelial cells to bind monocytes: difference to thromboxane‐mediated endothelial activation
Author(s) -
Leitinger Norbert,
Huber Joakim,
Rizza Cristina,
Mechtcheriakova Diana,
Bochkov Valery,
Koshelnick Yuri,
Berliner Judith A.,
Binder Bernd R.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0498fje
Subject(s) - isoprostane , chemistry , thromboxane , endothelial stem cell , thromboxane a2 , medicine , endocrinology , microbiology and biotechnology , platelet , biochemistry , biology , receptor , oxidative stress , in vitro , lipid peroxidation
Increased isoprostane levels were found in patients with vascular disease and in atherosclerotic lesions. Isoprostanes interact with vascular cells via thromboxane receptors (TPs) and block TP‐ reduced atherosclerosis in apoE‐deficient mice. This effect was, however, independent of thromboxane formation, suggesting involvement of isoprostanes. We investigated the stimulation of human endothelial cells (ECs) by the isoprostane 8‐iso‐PGF 2α with respect to induced monocyte adhesion, a key initiating event in atherogenesis. The isoprostane 8‐iso‐PGF 2α stimulated ECs to specifically bind monocytes. The TP agonist U46619 induced monocyte and neutrophil binding and expression of E‐selectin and vascular cell adhesion molecule‐1 (VCAM‐ 1). The monocyte adhesion induced by 8‐iso‐PGF 2α was independent of VCAM‐1 and could be blocked by a PKA (H89) and a MEK‐1 inhibitor (PD98059), whereas U46619‐induced monocyte adhesion was mediated by VCAM‐1 and could be blocked by a PKC inhibitor (bisindolylmaleimide I). The effects of 8‐iso‐PGF 2α and U46619 could be blocked by a TP antagonist and did not involve NF‐MB translocation but required activation of p38 MAPK . Our data demonstrate that 8‐iso‐PGF 2α induces monocyte adhesion in ECs by activating TPs or a TP‐ related receptor but via signaling mechanisms that are critically different from those activated by U46619. Therefore, generation of 8‐iso‐PGF 2α may induce atherosclerotic lesion formation by activation of ECs to bind monocytes.