RT Journal Article
T1 Activation of Peroxisome Proliferator Activator Receptor β/δ Improves Endothelial Dysfunction and Protects Kidney in Murine Lupus.
A1 Romero, Miguel
A1 Toral, Marta
A1 Robles-Vera, Iñaki
A1 Sanchez, Manuel
A1 Jimenez, Rosario
A1 O'Valle, Francisco
A1 Rodriguez-Nogales, Alba
A1 Perez-Vizcaino, Francisco
A1 Galvez, Julio
A1 Duarte, Juan
K1 acetylcholine
K1 blood pressure
K1 hypertension
K1 nephritis
K1 oxidative stress
K1 peroxisome
K1 proliferator-activated receptors
AB Women with systemic lupus erythematosus exhibit a high prevalence of hypertension, endothelial dysfunction, and renal injury. We tested whether GW0742, a peroxisome proliferator activator receptor β/δ (PPARβ/δ) agonist, ameliorates disease activity and cardiovascular complications in a female mouse model of lupus. Thirty-week-old NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with GW0742 or with the PPARβ/δ antagonist GSK0660 plus GW0742 for 5 weeks. Blood pressure, plasma double-stranded DNA autoantibodies and cytokines, nephritis, hepatic opsonins, spleen lymphocyte populations, endothelial function, and vascular oxidative stress were compared in treated and untreated mice. GW0742 treatment reduced lupus disease activity, blood pressure, cardiac and renal hypertrophy, splenomegaly, albuminuria, and renal injury in lupus mice, but not in control. GW0742 increased hepatic opsonins mRNA levels in lupus mice and reduced the elevated T, B, Treg, and Th1 cells in spleens from lupus mice. GW0742 lowered the higher plasma concentration of proinflammatory cytokines observed in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and increased nicotinamide adenine dinucleotide phosphate oxidase-driven vascular reactive oxygen species production, which were normalized by GW0742 treatment. All these effects of GW0742 were inhibited by PPARβ/δ blockade with GSK0660. Pharmacological activation of PPARβ/δ reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, which was associated with reduced plasma antidouble-stranded DNA autoantibodies and anti-inflammatory and antioxidant effects in target tissues. Our findings identify PPARβ/δ as a promising target for an alternative approach in the treatment of systemic lupus erythematosus and its associated vascular damage.
PB Lippincott Williams & Wilkins
YR 2017
FD 2017-06-30
LK http://hdl.handle.net/10668/10910
UL http://hdl.handle.net/10668/10910
LA en
NO Romero M, Toral M, Robles-Vera I, Sánchez M, Jiménez R, O'Valle F, et al. Activation of Peroxisome Proliferator Activator Receptor β/δ Improves Endothelial Dysfunction and Protects Kidney in Murine Lupus. Hypertension. 2017 Apr;69(4):641-650.
DS RISalud
RD Apr 8, 2025