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Role of Thromboxane A 2 Receptor on the Effects of Oxidized LDL on Microvascular Endothelium Nitric Oxide, Endothelin‐1, and IL‐6 Production
Author(s) -
LUBRANO VALTER,
BALDI SIMONA,
FERRANNINI ELE,
L'ABBATE ANTONIO,
NATALI ANDREA
Publication year - 2008
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680701884765
Subject(s) - nitric oxide , chemistry , thromboxane , enos , endocrinology , medicine , receptor , agonist , endothelin receptor , endothelin 1 , prostacyclin , nitric oxide synthase , biochemistry , platelet , biology , organic chemistry
Objective: The aim of this study was to determine to what extent thromboxane A 2 (TP) receptor mediates the effect of oxidated low‐density lipoprotein (LDL) on nitric oxide (NO), interleukin (IL)‐6, and endothelin‐1 (ET‐1) release by microvascular endothelial cells. Methods: Endothelial nitric oxide synthase (eNOS), nitrites and nitrates (NO 2 /NO 3 ), ET‐1, and IL‐6 production were measured following human microvascular endothelial cell 1 exposure to isoprostane‐8‐ epi ‐PGF 2α (F 2 IP), a natural agonist of the TP receptor present in oxidized LDL, or native, low‐, or medium‐oxidized LDL either with the TP‐receptor blocker, SQ29.548, or its vehicle. Results: F 2 IP and both native and oxidized LDL enhanced NO 2 /NO 3 . F 2 IP through the TP receptor stimulated eNOS (eight‐fold), while the oxidized LDL effect (two‐to five‐fold) was only partially prevented by SQ29.548. While LDL concentration and degree of oxidation synergistically and independent of SQ29.548 stimulated IL‐6, F 2 IP had no effect. F 2 IP induced a modest (+50%) increase in ET‐1. LDL, independent of concentration or degree of oxidation, stimulated (+120%) ET‐1 production, and this effect was only partially attenuated by SQ29.548. Conclusions: In microvascular endothelial cells, LDL concentration and degree of oxidation synergistically stimulate NO and IL‐6 production, but only NO release is largely mediated by the TP receptor. LDL facilitates ET‐1 release independent of concentration and degree of oxidation; TP‐receptor stimulation is only partially responsible for this effect.