Linked Life Data

16357304

Source:http://linkedlifedata.com/resource/pubmed/id/16357304

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-2-3
pubmed:abstractText
Increased reactive oxygen species (ROS) generation is implicated in cardiac remodeling in heart failure (HF). As xanthine oxidoreductase (XOR) is 1 of the major sources of ROS, we tested whether XOR inhibition could improve cardiac performance and induce reverse remodeling in a model of established HF, the spontaneously hypertensive/HF (SHHF) rat. We randomized Wistar Kyoto (WKY, controls, 18 to 21 months) and SHHF (19 to 21 months) rats to oxypurinol (1 mmol/L; n=4 and n=15, respectively) or placebo (n=3 and n=10, respectively) orally for 4 weeks. At baseline, SHHF rats had decreased fractional shortening (FS) (31+/-3% versus 67+/-3% in WKY, P<0.0001) and increased left-ventricular (LV) end-diastolic dimension (9.7+/-0.2 mm versus 7.0+/-0.4 mm in WKY, P<0.0001). Whereas placebo and oxypurinol did not change cardiac architecture in WKY, oxypurinol attenuated decreased FS and elevated LV end-diastolic dimension, LV end-systolic dimension, and LV mass in SHHF. Increased myocyte width in SHHF was reduced by oxypurinol. Additionally, fetal gene activation, altered calcium cycling proteins, and upregulated phospho-extracellular signal-regulated kinase were restored toward normal by oxypurinol (P<0.05 versus placebo-SHHF). Importantly, SHHF rats exhibited increased XOR mRNA expression and activity, and oxypurinol treatment reduced XOR activity and superoxide production toward normal, but not expression. On the other hand, NADPH oxidase activity remained unchanged, despite elevated subunit protein abundance in treated and untreated SHHF rats. Together these data demonstrate that chronic XOR inhibition restores cardiac structure and function and offsets alterations in fetal gene expression/Ca2+ handling pathways, supporting the idea that inhibiting XOR-derived oxidative stress substantially improves the HF phenotype.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16357304-Animals, pubmed-meshheading:16357304-Calcium-Transporting ATPases, pubmed-meshheading:16357304-Cardiomyopathy, Dilated, pubmed-meshheading:16357304-Enzyme Inhibitors, pubmed-meshheading:16357304-Gene Expression, pubmed-meshheading:16357304-Heart Failure, pubmed-meshheading:16357304-Myocardium, pubmed-meshheading:16357304-NADPH Oxidase, pubmed-meshheading:16357304-Oxidative Stress, pubmed-meshheading:16357304-Oxypurinol, pubmed-meshheading:16357304-Rats, pubmed-meshheading:16357304-Rats, Inbred SHR, pubmed-meshheading:16357304-Rats, Inbred WKY, pubmed-meshheading:16357304-Reactive Oxygen Species, pubmed-meshheading:16357304-Sarcoplasmic Reticulum Calcium-Transporting ATPases, pubmed-meshheading:16357304-Ventricular Remodeling, pubmed-meshheading:16357304-Xanthine Oxidase
pubmed:year
2006
pubmed:articleTitle
Xanthine oxidoreductase inhibition causes reverse remodeling in rats with dilated cardiomyopathy.
pubmed:affiliation
Cardiology Division, Department of Medicine, Institute for Cell Engineering, Johns Hopkins Medical Institutions, Baltimore, MD 21212, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural