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- _4 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _3 value "Central to the pathophysiology of sickle cell disease are the vaso-occlusive events which lead to tissue damages and life threatening complications. Lungs are particularly vulnerable to vaso-occlusion because of their specific vasculature. We developed a mouse model of hypoxia/reoxygenation lung injury closely mimicking the lung pathology of human sickle cell patients. This model involves the exposure of SAD transgenic sickle mice to hypoxia (8% oxygen) for 4, 10, 46 hours followed by 2 hours reoxygenation. Gene expression profiling of SAD lung tissue pointed to the specific induction of genes involved in the response to ischemic stress and microcirculation remodeling: Hspcb, Hsp86-1, Nfe2l2, Ace and Fgf7. Hypoxia/reoxygenation also induced a marked increase in bronchoalveolar (BAL) total leukocyte and neutrophil counts, BAL total protein content and BAL TNF- alpha, IL-6, IL1alpha and MIP-2 levels, all indicators of enhanced inflammatory response as compared to control mice. Nitric oxide (NO) was administered to SAD mice. NO (40 ppm) inhalation protected SAD mice from the histopathological lesions of ischemic/reperfusion lung injury with corresponding normalization and/or modulation of tissue gene expression profiles. Inhaled NO: (i) significantly reduced the increase in BAL total protein content, BAL total leukocyte and neutrophil counts; (ii) modulated BAL cytokine network and (ii) did not affect hemoglobin and methemoglobin levels. The present study provides evidences for the beneficial effects of inhaled NO in pulmonary injury induced by hypoxia/reoxygenation in a mouse model of SCD and opens new avenues in drug design based upon tissue gene expression profiling." provenance.
- _3 wasQuotedFrom 12689931 provenance.
- assertion hadPrimarySource 12689931 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom _3 provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- large_corpus.bel authoredBy _4 provenance.
- large_corpus.bel version "20131211" provenance.