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The PPARgamma Agonist Rosiglitazone Decreases Blood Pressure and Renal Injury in a Female Mouse Model of Systemic Lupus Erythematosus
Author(s) -
VenegasPont Marcia,
Maric Christine,
McLemore Gerald R.,
Glover Porter,
Ryan Michae J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.969.22
Subject(s) - medicine , rosiglitazone , endocrinology , albuminuria , agonist , glomerulosclerosis , systemic lupus erythematosus , renal injury , proteinuria , kidney , receptor , disease
Women with the inflammatory autoimmune disorder systemic lupus erythematosus (SLE) exhibit a high incidence of hypertension and renal injury. Peroxisome proliferator activated receptor gamma (PPARγ) activation has anti‐inflammatory and anti‐hypertensive effects. We tested whether the PPARγ agonist rosiglitazone (Rosi) prevents hypertension and renal injury in a female mouse model of SLE (NZBWF1). 30 week old SLE and control (NZW/LacJ) mice (n≥ 7 per group) were fed either Rosi (5mg/kg/day in standard chow) or unsupplemented chow for 4 weeks. Renal injury was assessed using the glomerulosclerosis index (GSI) and a positive urinary albumin test ≥100 mg/dL, Albustix). MAP, measured by indwelling catheters, was increased in SLE mice compared to controls (139±4 vs. 112±4, p<0.05). Rosi treatment significantly lowered MAP in SLE mice (127±4, p<0.05) but had no effect in control mice (111±4 mmHg). Anti‐DNA auto‐antibodies, a marker for SLE, did not differ in vehicle or Rosi treated SLE mice (756±157 vs 762±251 ng/ml). Only 18% of Rosi treated SLE mice exhibited albuminuria compared to 42% of vehicle treated SLE mice. Mice with SLE had increased GSI compared with controls (1.9±0.6 vs 0.6±0.1, p<0.05). Preliminary data indicate that GSI is reduced in Rosi treated SLE mice (1.0±0.2) with no effect in control mice (0.7±0.1). These data implicate PPARγ as a potential therapeutic target for the treatment hypertension and renal end‐organ damage associated with SLE. (supported by R01HL085907 MJR)