Protective effects of<i>S</i>-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease

Franceschi, Lucia De; Malpeli, Giorgio; Scarpa, Aldo; Janin, Anne; Muchitsch, Eva-Maria; Roncada, Paola; Lebœuf, Christophe; Corrocher, Roberto; Beuzard, Yves; Brugnara, Carlo

doi:10.1152/ajplung.00462.2005

Cited by 31 publications

(23 citation statements)

References 42 publications

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“…This may explain in part why SAD mice experience little spontaneous VOC without a hypoxic challenge. Nevertheless, NO administration has been shown to inhibit VOC-induced lung damage in the same model of H/R-induced VOC (20,43). These various observations suggest that an imbalance between ET-1 and NO plays a critical role in SCD.…”

Section: Figurementioning

confidence: 96%

Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease

Sabaa¹,

Franceschi²,

Bonnin³

et al. 2008

J. Clin. Invest.

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124

129

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Patients with sickle-cell disease (SCD) suffer from tissue damage and life-threatening complications caused by vasoocclusive crisis (VOC). Endothelin receptors (ETRs) are mediators of one of the most potent vasoconstrictor pathways in mammals, but the relationship between vasoconstriction and VOC is not well understood. We report here that pharmacological inhibition of ETRs prevented hypoxia-induced acute VOC and organ damage in a mouse model of SCD. An in vivo ultrasonographic study of renal hemodynamics showed a substantial increase in endothelin-mediated vascular resistance during hypoxia/reoxygenation-induced VOC. This increase was reversed by administration of the dual ETR antagonist (ETRA) bosentan, which had pleiotropic beneficial effects in vivo. It prevented renal and pulmonary microvascular congestion, systemic inflammation, dense rbc formation, and infiltration of activated neutrophils into tissues with subsequent nitrative stress. Bosentan also prevented death of sickle-cell mice exposed to a severe hypoxic challenge. These findings in mice suggest that ETRA could be a potential new therapy for SCD, as it may prevent acute VOC and limit organ damage in sickle-cell patients.

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Section: Figurementioning

confidence: 96%

Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease

Sabaa¹,

Franceschi²,

Bonnin³

et al. 2008

J. Clin. Invest.

Self Cite

124

129

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“…Similarly, increased plasma SNO levels, suggestive of impaired NO delivery or excessive NO sequestration, are associated with adverse cardiovascular outcomes and hypertension in end-stage renal disease patients106, and misappropriation of NO as SNO-albumin is also directly implicated in the pathogenesis of hypertension in preeclampsia107, 108. It is important to emphasize, however, that exogenously administered SNO-albumin has been shown to serve as an effective therapeutic agent in a number of animal models including ischaemia/reperfusion-associated heart damage109, 110, lung injury in sickle cell disease111 and cardiopulmonary dysfunction in endotoxemia112, 113.…”

Section: Roles Of S-nitrosylation In Vascular Signalingmentioning

confidence: 99%

S -Nitrosylation in Cardiovascular Signaling

Lima

Forrester

Hess

et al. 2010

Circulation Research

463

386

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Key Words: angiogenesis Ⅲ apoptosis Ⅲ atherosclerosis Ⅲ cardiac electrophysiology Ⅲ excitation-contraction coupling Ⅲ adrenergic contractility M olecular oxygen (O 2 ) and carbon dioxide (CO 2 ) are critical components of cardiovascular physiology (and pathophysiology). These gaseous molecules are central to tissue physiology and cellular respiration, and it has long been understood that disturbances in O 2 or CO 2 processing are both causative and indicative of pathophysiology. 1 Over time, however, it has become increasingly clear that nitric oxide (NO) is also an endogenous regulator in cardiovascular physiology and cellular respiration, operating at considerably lower concentrations than O 2 or CO 2 . These observations have led to the proposal that NO is the "third gas" of the respiratory cycle. [2][3][4] The major sources of NO in vivo are the NO synthase (NOS) isoforms. These include predominantly the neuronal Original

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“…19,26 The percentage of neutrophils was determined on cytospin centrifugation. The remaining BAL samples were centrifuged at 1,500 x g for 10 min at 4°C.…”

Section: Bronchoalveolar Lavage Measurementsmentioning

confidence: 99%

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

et al. 2015

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The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a ω-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease. ABSTRACTmice. 16,17 The animal protocol was approved by the Animal Care and Use Committee of the University of Verona (CIRSAL). Twomonth old animals were fed for 6 weeks with either the standard AIN-93M purified rodent diet (soy-diet with n6/n3 ratio of 8:1 -Dyets Inc., Bethlehem, PA, USA), containing 140 g/kg casein, 1.8 g/kg L-cystine, 100 g/kg sucrose, 465.9 g/kg cornstarch, 155 g/kg dextrose, 40 g/kg soybean oil, 0.8 mg/kg t-butylhydroquinone, 50 g/kg cellulose, 35 g/kg mineral mix, 10 g/kg vitamin mix, and 2.5 g/kg choline bitartrate 18 or the ω-3 FD, an AIN-93M-based purified rodent diet in which all of the calories provided by fat (10%) are replaced by 7.9% from HCO and 2.1% from ω-3 oil (Dyets Inc., Bethlehem, PA, USA). At the end of the 6 weeks of FD supplementation, animals were anesthetized with isofluorane, and whole blood was collected from each mouse via retro-orbital venipuncture by heparinized microcapillaries. Mice were euthanized and organs removed immediately. The organs were divided into two and either frozen immediately in liquid nitrogen or fixed in 10% formalin and embedded in paraffin for histology. Whenever indicated, 6-week old mice were exposed to hypoxia (8% oxygen for 10 h) followed by 3 h of reoxygenation (21% oxygen) (H/R stress) to mimic an acute VOC, as previously described.

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Protective effects ofS-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease

Cited by 31 publications

References 42 publications

Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease

Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease

S -Nitrosylation in Cardiovascular Signaling

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

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