TY - JOUR
T1 - Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus
AU - Venegas-Pont, Marcia
AU - Sartori-Valinotti, Julio C.
AU - Maric, Christine
AU - Racusen, Lorraine C.
AU - Glover, Porter H.
AU - McLemore, Gerald R.
AU - Jones, Allison V.
AU - Reckelhoff, Jane F.
AU - Ryan, Michael J.
PY - 2009/4
Y1 - 2009/4
N2 - Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARγ) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n ≥ 6/group) were fed Rosi (5 mg·kg -1 ·day-1 in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 ± 4 vs. 111 ± 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 ± 4, P < 0.05) but not in controls (111 ± 4). Urinary albumin (μg/mg creatinine) was increased in SLE mice compared with controls (12,396 ± 6,525 vs. 50 ± 6) and reduced with Rosi treatment (148 ± 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 ± 1.6 vs. 0.4 ± 0.3, P < 0.05). Renal monocyte/ macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 ± 11.0 vs. 10.6 ± 3.6, P < 0.05) but unchanged in controls (3.7 ± 1.6 vs. 3.7 ± 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 ± 0.59 vs. 0.6 ± 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 ± 0.11, P < 0.05). PPARγ protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.
AB - Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARγ) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n ≥ 6/group) were fed Rosi (5 mg·kg -1 ·day-1 in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 ± 4 vs. 111 ± 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 ± 4, P < 0.05) but not in controls (111 ± 4). Urinary albumin (μg/mg creatinine) was increased in SLE mice compared with controls (12,396 ± 6,525 vs. 50 ± 6) and reduced with Rosi treatment (148 ± 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 ± 1.6 vs. 0.4 ± 0.3, P < 0.05). Renal monocyte/ macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 ± 11.0 vs. 10.6 ± 3.6, P < 0.05) but unchanged in controls (3.7 ± 1.6 vs. 3.7 ± 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 ± 0.59 vs. 0.6 ± 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 ± 0.11, P < 0.05). PPARγ protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.
KW - Endothelin
KW - Glomerulosclerosis
KW - Inflammation
KW - Lupus
KW - Proliferator activated receptor gamma
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U2 - 10.1152/ajpregu.90992.2008
DO - 10.1152/ajpregu.90992.2008
M3 - Article
C2 - 19193937
AN - SCOPUS:65949088801
SN - 0363-6119
VL - 296
SP - R1282-R1289
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -