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 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 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 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

Myocardial Infarction in Systemic Lupus Erythematosus – the Sex Specific Risk Profile

2020 ◽  
Vol 26 ◽  
Author(s):  
Marija Vavlukis ◽  
Daniela Pop-Gjorceva ◽  
Lidija Poposka ◽  
Emilija Sandevska ◽  
Sasko Kedev
Keyword(s):  
Myocardial Infarction ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Systemic Lupus ◽  
Antiinflammatory Therapy

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review is to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and development of atherosclerosis at an earlier age. Contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3- fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or antiinflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although Systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcome. Method: We conducted a literature review through PubMed and Cochrane, using key words: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics.

scholarly journals Body composition and basal metabolic rate in systemic lupus erythematosus patients

2017 ◽  
Vol 39 (2) ◽  
pp. 99-102 ◽  
Author(s):  
Z. Shamekhi ◽  
Z. Habibagahi ◽  
M. Ekramzadeh ◽  
Ata Ghadiri ◽  
F. Namjoyan ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Body Composition ◽  
Metabolic Rate ◽  
Basal Metabolic Rate ◽  
Lupus Erythematosus ◽  
Systemic Lupus

scholarly journals Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (12) ◽  
pp. 2286-2293 ◽  
Author(s):  
ADNAN N. KIANI ◽  
JENS VOGEL-CLAUSSEN ◽  
ARMIN ARBAB-ZADEH ◽  
LAURENCE S. MAGDER ◽  
JOAO LIMA ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Lupus Erythematosus ◽  
Univariate Analysis ◽  
Coronary Plaque ◽  
Systemic Lupus ◽  
History Of ◽  
Noncalcified Plaque

Objective.A major cause of morbidity and mortality in systemic lupus erythematosus (SLE) is accelerated coronary atherosclerosis. New technology (computed tomographic angiography) can measure noncalcified coronary plaque (NCP), which is more prone to rupture. We report on a study of semiquantified NCP in SLE.Methods.Patients with SLE (n = 147) with no history of cardiovascular disease underwent 64-slice coronary multidetector computed tomography (MDCT). The MDCT scans were evaluated quantitatively by a radiologist, using dedicated software.Results.The group of 147 patients with SLE was 86% female, 70% white, 29% African American, and 3% other ethnicity. The mean age was 51 years. In our univariate analysis, the major traditional cardiovascular risk factors associated with noncalcified plaque were age (p = 0.007), obesity (p = 0.03; measured as body mass index), homocysteine (p = 0.05), and hypertension (p = 0.04). Anticardiolipin (p = 0.026; but not lupus anticoagulant) and anti-dsDNA (p = 0.03) were associated with higher noncalcified plaque. Prednisone and hydroxychloroquine therapy had no effect, but methotrexate (MTX) use was associated with higher noncalcified plaque (p = 0.0001). In the best multivariate model, age, current MTX use, and history of anti-dsDNA remained significant.Conclusion.Our results suggest that serologic SLE (anti-dsDNA) and traditional cardiovascular risk factors contribute to semiquantified noncalcified plaque in SLE. The association with MTX is not understood, but should be replicated in larger studies and in multiple centers.

scholarly journals Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

2016 ◽  
Vol 113 (38) ◽  
pp. 10637-10642 ◽  
Author(s):  
Elaine V. Lourenço ◽  
Aijing Liu ◽  
Giuseppe Matarese ◽  
Antonio La Cava
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
New Zealand ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Cellular Level ◽  
Presentation Of Self ◽  
Systemic Lupus ◽  
Autoantibody Production

Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.

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