| First Author | Gao Z | Year | 2014 |
| Journal | Biochem Pharmacol | Volume | 91 |
| Issue | 4 | Pages | 474-82 |
| PubMed ID | 25149102 | Mgi Jnum | J:215377 |
| Mgi Id | MGI:5605200 | Doi | 10.1016/j.bcp.2014.08.009 |
| Citation | Gao Z, et al. (2014) Cyclooxygenase-2-dependent oxidative stress mediates palmitate-induced impairment of endothelium-dependent relaxations in mouse arteries. Biochem Pharmacol 91(4):474-82 |
| abstractText | Palmitic acid, one of the saturated free fatty acids, impairs cardiovascular function as manifested by inducing vascular inflammation, apoptosis and over-production of reactive oxygen species (ROS) although the origin for ROS remains unclear. The present study investigated the cellular mechanisms underlying palmitate-induced impairment of endothelial function. Ex vivo treatment in tissue culture with palmitate concentration-dependently attenuated acetylcholine-induced endothelium-dependent relaxations, up-regulated the expression of cyclooxygenase-2 (COX-2) and elevated superoxide formation in mouse aortic endothelial cells (MAECs) measured by dihydroethidium (DHE) staining and electron paramagnetic resonance (EPR) spectroscopy. Superoxide scavengers, COX-2 inhibitor and thromboxane prostanoid (TP) receptor antagonist, but not COX-1 inhibitor reversed the harmful effects of palmitate. Furthermore, palmitate impaired acetylcholine-induced relaxations and raised superoxide in en face endothelium of aortas only from COX-1(-/-) mice but not from COX-2(-/-) mice. Palmitate increased the production and release of TXB2, a stable thromboxane A2 metabolite in mouse aortas, which was abolished by COX-2 inhibitor. Superoxide scavenger did not affect palmitate-induced up-regulated expression of COX-2 in MAECs. Both real time PCR and luciferase reporter gene assay confirmed COX-2 up-regulation in palmitate-treated MAECs and NF-kappaB was substantially involved in this up-regulation. The present study provides novel evidence that palmitate up-regulates COX-2 through NF-kappaB-dependent mechanism and resultant COX-2-associated oxidative stress impairs endothelium-dependent relaxations in mouse aortas. |
