scholarly journals The PPARgamma Agonist Rosiglitazone Decreases Blood Pressure and Renal Injury in a Female Mouse Model of Systemic Lupus Erythematosus

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Marcia Venegas‐Pont ◽  
Christine Maric ◽  
Gerald R. McLemore ◽  
Porter Glover ◽  
Michae J. Ryan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Female Mouse ◽  
Systemic Lupus

scholarly journals Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

2009 ◽  
Vol 296 (4) ◽  
pp. R1282-R1289 ◽  
Author(s):  
Marcia Venegas-Pont ◽  
Julio C. Sartori-Valinotti ◽  
Christine Maric ◽  
Lorraine C. Racusen ◽  
Porter H. Glover ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Female Mouse ◽  
Therapeutic Option ◽  
Peroxisome Proliferator ◽  
Systemic Lupus ◽  
Pparγ Agonist

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−1in 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.

scholarly journals Human recombinant relaxin-2 does not attenuate hypertension or renal injury but exacerbates vascular dysfunction in a female mouse model of SLE

2019 ◽  
Vol 317 (2) ◽  
pp. H234-H242
Author(s):  
Victoria L. Wolf ◽  
Taylor L. Phillips ◽  
Erin B. Taylor ◽  
Jennifer M. Sasser ◽  
Michael J. Ryan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mouse Model ◽  
Experimental Model ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Female Mouse ◽  
Vascular Dysfunction ◽  
Therapeutic Effects ◽  
Systemic Lupus ◽  
Relaxin 2

Systemic lupus erythematosus (SLE) is an autoimmune disease that disproportionately affects women of reproductive age and increases their risk for developing hypertension, vascular, and renal disease. Relaxin has potential beneficial therapeutic effects in cardiovascular disease through direct actions on the vasculature. The potential therapeutic benefit of relaxin on SLE-associated cardiovascular and renal risk factors like hypertension has not previously been tested. We hypothesized that relaxin would attenuate hypertension, renal injury, and vascular dysfunction in an established female mouse model of SLE (NZBWF1 mice). Serelaxin (human recombinant relaxin-2, 0.5 mg·kg−1·day−1) or vehicle was administered via osmotic mini-pump for 4 wk in female control (NZW) or SLE mice between 28 and 31 wk of age. Serelaxin treatment increased uterine weights in both groups, suggesting that the Serelaxin was bioactive. Mean arterial pressure, measured by carotid artery catheter, was significantly increased in vehicle-treated SLE mice compared with vehicle-treated controls, but was not changed by Serelaxin treatment. Albumin excretion rate, measured by ELISA, was similar between vehicle- and Serelaxin-treated SLE mice and between vehicle- and Serelaxin-treated control mice. Wire myography was performed using isolated carotid arteries to assess endothelial-independent and -dependent vasodilation, and data confirm that SLE mice have impaired endothelium-independent and -dependent relaxation compared with control mice. Serelaxin treatment did not affect endothelium-independent vasodilation, but exacerbated the endothelium-dependent dysfunction. These data suggest that, contrary to our hypothesis, Serelaxin infusion does not attenuate hypertension, renal injury, or vascular dysfunction in SLE, but worsens underlying vascular endothelial dysfunction in this experimental model of SLE. These data do not support the use of human recombinant relaxin-2 as an antihypertensive in the SLE patient population. NEW & NOTEWORTHY Relaxin is a peptide hormone commonly known for its role in pregnancy and for its use in recent clinical trials for the treatment of heart failure. Evidence suggests that relaxin has immunomodulatory effects; however, the potential therapeutic impact of relaxin in chronic immune mediated disease is unclear. This study tests whether recombinant human relaxin (Serelaxin) attenuates the progression of autoimmunity, and the associated cardiovascular consequences, in an experimental model of systemic lupus erythematosus.

scholarly journals Tumor Necrosis Factor-α Antagonist Etanercept Decreases Blood Pressure and Protects the Kidney in a Mouse Model of Systemic Lupus Erythematosus

Hypertension ◽  
2010 ◽  
Vol 56 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Marcia Venegas-Pont ◽  
Michaele B. Manigrasso ◽  
Samira C. Grifoni ◽  
Babbette B. LaMarca ◽  
Christine Maric ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Systemic Lupus ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Blood pressure and renal hemodynamic responses to acute angiotensin II infusion are enhanced in a female mouse model of systemic lupus erythematosus

2011 ◽  
Vol 301 (5) ◽  
pp. R1286-R1292 ◽  
Author(s):  
Marcia Venegas-Pont ◽  
Keisa W. Mathis ◽  
Radu Iliescu ◽  
William H. Ray ◽  
Porter H. Glover ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Female Mouse ◽  
Receptor Expression ◽  
Ang Ii ◽  
Systemic Lupus ◽  
Hemodynamic Responses ◽  
Immune System Dysfunction ◽  
Renal Hemodynamic

Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II.

Lactobacillus fermentum CECT5716 prevents renal damage in the NZBWF1 mouse model of systemic lupus erythematosus

2020 ◽  
Vol 11 (6) ◽  
pp. 5266-5274 ◽  
Author(s):  
Néstor de la Visitación ◽  
Iñaki Robles-Vera ◽  
Marta Toral ◽  
Francisco O'Valle ◽  
Javier Moleon ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Female Mouse ◽  
Renal Damage ◽  
Lactobacillus Fermentum ◽  
Systemic Lupus

The aim of this work was to evaluate whether the immune-modulatory bacterium Lactobacillus fermentum CECT5716 (LC40) protects the kidneys in a female mouse model of lupus with hypertension.

scholarly journals Hypertension in an experimental model of systemic lupus erythematosus occurs independently of the renal nerves

2013 ◽  
Vol 305 (7) ◽  
pp. R711-R719 ◽  
Author(s):  
Keisa W. Mathis ◽  
Marcia Venegas-Pont ◽  
Elizabeth R. Flynn ◽  
Jan Michael Williams ◽  
Christine Maric-Bilkan ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Renal Denervation ◽  
Renal Nerves ◽  
Inflammatory Disorder ◽  
Systemic Lupus ◽  
Chronic Inflammatory Disorder ◽  
And Control

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with prevalent hypertension and renal injury. In this study, we tested whether the renal nerves contribute to the development of hypertension in an established mouse model of SLE ( NZBWF1). Female SLE and control ( NZW/LacJ) mice were subjected to either bilateral renal denervation or a sham procedure at 32 wk of age. Two weeks later, blood pressure was assessed in conscious mice using carotid artery catheters. Blood pressure was higher in SLE mice compared with controls, as previously reported; however, blood pressure was not altered in the denervated SLE or control mice. The development of albuminuria was markedly blunted in denervated SLE mice; however, glomerulosclerosis was increased. Renal denervation reduced renal cortical expression of monocyte-chemoattractant protein in SLE mice but did not significantly alter renal monocyte/macrophage infiltration. Renal cortical TNF-α expression was also increased in sham SLE mice, but this was not impacted by denervation. This study suggests that the renal nerves do not have a significant role in the pathogenesis of hypertension, but have a complex effect on the associated renal inflammation and renal injury.

scholarly journals Impact of early life ovariectomy on blood pressure and body composition in a female mouse model of systemic lupus erythematosus

2014 ◽  
Vol 307 (8) ◽  
pp. R990-R997 ◽  
Author(s):  
Emily L. Gilbert ◽  
Michael J. Ryan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Body Composition ◽  
Body Weight ◽  
Cardiovascular Risk ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Early Life ◽  
Systemic Lupus ◽  
Autoantibody Production

Because of the preponderance of women affected by the chronic autoimmune disease systemic lupus erythematosus (SLE), estrogen is thought to contribute to SLE disease progression. This is supported by evidence from experimental animal models of SLE showing that removal of estrogen in young female mice delays autoantibody production and renal injury and lengthens survival. Blood pressure and changes in body composition are important cardiovascular risk factors that can be regulated by estrogens. Because cardiovascular disease is the leading cause of death in patients with SLE, we used an established female mouse model of SLE (NZBWF1) to test whether early life removal of estrogen impacts the development of hypertension and changes in body composition commonly associated with SLE. Eight-week-old female SLE and control mice (NZW/LacJ) underwent either a sham operation or ovariectomy. Body weight, body composition (fat and lean masses), and renal injury (albuminuria) were monitored until mice reached 34 wk of age, at which time mean arterial pressure was assessed in conscious animals by a carotid catheter. Early life removal of the ovaries delayed the onset of autoantibody production and albuminuria while causing an increase in body weight and fat mass. Blood pressure in the adult was not altered by early life removal of the ovaries. These data suggest that estrogens may have a permissive role for the development of SLE while helping to maintain normal body weight and composition, which is associated with reduced cardiovascular risk.

scholarly journals SAT0211 RENAL INJURY IN SYSTEMIC LUPUS ERYTHEMATOSUS CHARACTERIZED BY THROMBOTIC MICROANGIOPATHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1048.1-1048
Author(s):  
W. Hu
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Renal Injury ◽  
Renal Outcome ◽  
Pathological Examination ◽  
Systemic Lupus ◽  
Tubulointerstitial Lesions

Background:Classical lupus nephritis (LN) is characterized by glomerular immune complex(IC) deposition with glomerular proliferation, basement membrane destruction and cell infiltration. Non-IC mediated renal injury with thrombotic microangiopathy (TMA) was also reported in patients with systemic lupus erythematosus (SLE-renal TMA), but most studies were reported in patients with both LN and renal TMA.Objectives:In this study, clinical features and outcomes of SLE-renal TMA in absence of obvious IC in SLE patients were analyzed.Methods:Patients with glomerular TMA and/or vascular TMA in the absence of obvious subendothelial or epithelial immune deposits were screened out from 2332 biopsied in SLE patients who underwent first renal biopsy from January 2005 to August 2016. Their clinical, histological features and outcomes were retrospectively analyzed.Results:In 2332 renal biopsies obtained from SLE patients, 257 (11.0%) showed renal TMA, of which 237 showed both renal TMA and LN, and 20 biopsies had only renal TMA (SLE-renal TMA). There were 2 males and 18 females with an average age of (25 ± 10) years. The median course of SLE and LN were 3.0(1.0, 6.0) and 0.8(0.5, 1.9) months. All 20 patients deserved acute kidney injury, of which 11 (55%) needed renal replacement therapy (RRT) and 12 (60%) were nephrotic syndrome. Blood system involvement was found in all cases, including 13 cases (65.0%) with TMA triad (microvascular hemolytic anemia, thrombocytopenia and elevated lactate dehydrogenase).Pathological examination showed that 17 cases (85.0%) had both glomerular TMA and vascular TMA. Immunofluorescence and electron microscopy showed that 8 cases (40%) had no IC deposition in glomerulus and 12 cases (60%) had only IC deposition in mesangium. Acute tubulointerstitial lesions in patients requiring RRT were more serious than those no needing for RRT((43.6±24.9) %vs(21.7±20.1) %,P=0.047). The fusion range of foot process was positively correlated with proteinuria (r2= 0.347,P=0.006).All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange and three patients received gamma globulin, respectively. Eleven patients requiring RRT all stop RRT in a median time of 16.0 (9.0, 30.0) days. During a median follow-up of 58.0 (36.0, 92.3) months, complete remission (CR) was obtained in 15 cases, partial remission in 4 cases and no remission in 1 case. Six cases (30%) relapsed. No case died or progressed to end stage renal disease.Conclusion:Renal injury characterized by TMA is not uncommon in SLE renal biopsy cases. The clinical manifestation is special and the renal injury is serious. The renal outcome is good by intensive immunosuppressive therapy. It should be considered as a unique type of renal injury in SLE.References:[1]Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002. 347(8): 589-600.[2]Anders HJ, Weening JJ. Kidney disease in lupus is not always ‘lupus nephritis’. Arthritis Res Ther. 2013. 15(2): 108.[3]Song D, Wu LH, Wang FM, et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther. 2013. 15(1): R12.[4]Hu WX, Liu ZZ, Chen HP, Zhang HT, Li LS, Liu ZH. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010. 19(14): 1591-8.[5]Tomov S, Lazarchick J, Self SE, Bruner ET, Budisavljevic MN. Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim. Lupus. 2013. 22(5): 504-9.[6]Li C, Yap D, Chan G, et al. Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy. J Rheumatol. 2019 .[7]Chen MH, Chen MH, Chen WS, et al. Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan. Rheumatology (Oxford). 2011. 50(4): 768-75.[8]Park MH, AUID- Oho, Caselman N, Ulmer S, Weitz IC, AUID- Oho. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv. 2018. 2(16): 2090-2094.Disclosure of Interests:None declared

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