| Autor: |
Limor, Rona, Sharon, Orly, Knoll, Esther, Many, Ariel, Weisinger, Gary, Stern, Naftali |
| Předmět: |
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| Zdroj: |
American Journal of Hypertension; Feb2008, Vol. 21 Issue 2, p219-223, 5p, 1 Chart, 5 Graphs |
| Abstrakt: |
BACKGROUND Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor family that has been implicated in cell differentiation and proliferation, glucose metabolism, macrophage development, and inflammatory responses. PPAR-γ can be activated by a range of synthetic substances and also by products of lipid oxidation such as oxidized low-density lipoprotein, 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE). Since 12- and 15-lipoxygenase (12- and 15-LO) are expressed in human vascular smooth muscle cells (VSMCs), we set out to investigate the possible relation between PPAR-γ and LO system in these cells. METHODS In vitro experiments in human VSMC using standard methods. RESULTS The LO products, 12-HETE (10-7 mol/l), 15-HETE (10-7 mol/l) and 13-HODE (10-7 mol//l) increased the expression of PPAR-γ-2 messenger RNA (mRNA) in VSMC (by 100, 50, and 100%, respectively. Rosiglitazone (1-10 μmol/l) was found to upregulate both the mRNA expression of two LO enzymes, platelet-type 12-lipoxygenase (12-LO; +70%) and 15-lipoxygenase type 2 (15-LO; +60%), and the secretion of their eicosanoid products 12- and 15-HETE. In addition, rosiglitazone-induced a threefold increase in PPAR-γ-2 mRNA expressions and modest 50% rise in PPAR-γ-1 mRNA expression. The effect of rosiglitazone on PPAR-γ-2 could be entirely blocked by the LO inhibitor baicalein and restored by the addition of exogenous 12-HETE. CONCLUSIONS These results suggest a novel amplification cycle in which PPAR-γ activation induces production of 12- and 15-LO-derived metabolites which in turn feed back to upregulate PPAR-γ-2's own expression. The implications of this link in VSMC pathophysiology remain to be elucidated. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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