Linked Life Data

18261470

Source:http://linkedlifedata.com/resource/pubmed/id/18261470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-4-4
pubmed:abstractText
Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by microvascular vaso-occlusion with erythrocytes containing polymerized sickle (S) hemoglobin, erythrocyte hemolysis, vasculopathy, and both acute and chronic multiorgan injury. It is associated with steady state increases in plasma cell-free hemoglobin and overproduction of reactive oxygen species (ROS). Hereditary and acquired hemolytic conditions release into plasma hemoglobin and other erythrocyte components that scavenge endothelium-derived NO and metabolize its precursor arginine, impairing NO homeostasis. Overproduction of ROS, such as superoxide, by enzymatic (xanthine oxidase, NADPH oxidase, uncoupled eNOS) and nonenzymatic pathways (Fenton chemistry), promotes intravascular oxidant stress that can likewise disrupt NO homeostasis. The synergistic bioinactivation of NO by dioxygenation and oxidation reactions with cell-free plasma hemoglobin and ROS, respectively, is discussed as a mechanism for NO resistance in SCD vasculopathy. Human physiological and transgenic animal studies provide experimental evidence of cardiovascular and pulmonary resistance to NO donors and reduced NO bioavailability that is associated with vasoconstriction, decreased blood flow, platelet activation, increased endothelin-1 expression, and end-organ injury. Emerging epidemiological data now suggest that chronic intravascular hemolysis is associated with certain clinical complications: pulmonary hypertension, cutaneous leg ulcerations, priapism, and possibly stroke. New therapeutic strategies to limit intravascular hemolysis and ROS generation and increase NO bioavailability are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1506-28
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Sickle cell disease vasculopathy: a state of nitric oxide resistance.
pubmed:affiliation
Vascular Medicine Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural