RT Journal Article
T1 Role of endoplasmic reticulum stress in the protective effects of PPARβ/δ activation on endothelial dysfunction induced by plasma from patients with lupus.
A1 Toral, Marta
A1 Jiménez, Rosario
A1 Romero, Miguel
A1 Robles-Vera, Iñaki
A1 Sánchez, Manuel
A1 Salaices, Mercedes
A1 Sabio, José Mario
A1 Duarte, Juan
K1 Endoplasmic reticulum
K1 Endothelial dysfunction
K1 PPARβ/δ
K1 Systemic lupus erythematosus
AB We tested whether GW0742, a peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) agonist, improves endothelial dysfunction induced by plasma from patients with systemic lupus erythematosus (SLE) involving the inhibition of endoplasmic reticulum (ER) stress. A total of 12 non-pregnant women with lupus and 5 non-pregnant healthy women (controls) participated in the study. Cytokines and double-stranded DNA autoantibodies (anti-dsDNA) were tested in plasma samples. Endothelial cells, isolated from human umbilical cord veins (HUVECs), were used to measure nitric oxide (NO), intracellular reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and ER stress markers. Interferon-γ, interleukin-6, and interleukin-12 levels were significantly increased in plasma from patients with SLE with active nephritis (AN), as compared to both patients with SLE with inactive nephritis (IN) and the control group. The NO production stimulated by both the calcium ionophore A23187 and insulin was significantly reduced in HUVECs incubated with plasma from patients with AN-SLE as compared with the control group. Plasma from patients with IN-SLE did not modify A23187-stimulated NO production. Increased ROS production and NADPH oxidase activity were found in HUVECs incubated with plasma from patients with AN-SLE, which were suppressed by the ER stress inhibitor 4-PBA and the NADPH oxidase inhibitors, apocynin and VAS2870. GW0742 incubation restored the impaired NO production, the increased ROS levels, and the increased ER stress markers induced by plasma from patients with AN-SLE. These protective effects were abolished by the PPARβ/δ antagonist GSK0660 and by silencing PPARβ/δ. PPARβ/δ activation may be an important target to control endothelial dysfunction in patients with SLE.
YR 2017
FD 2017-12-06
LK http://hdl.handle.net/10668/11878
UL http://hdl.handle.net/10668/11878
LA en
DS RISalud
RD Apr 8, 2025