Linked Life Data

17583724

Source:http://linkedlifedata.com/resource/pubmed/id/17583724

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-7-23
pubmed:abstractText
The cytoskeletal protein dystrophin has been implicated in hereditary and acquired forms of cardiomyopathy. However, much remains to be learned about the role of dystrophin in the heart. We hypothesized that the dystrophin-deficient heart displays early alterations in energy metabolism that precede overt cardiomyopathy. We evaluated the metabolic and functional phenotype of dystrophin-deficient mdx mouse hearts at 10-12 weeks, when no major histological or echocardiographic abnormalities are reported. Ex vivo working mdx heart perfusions with stable isotopes revealed a marked shift in substrate fuel selection from fatty acids to carbohydrates associated with enhanced oxygen consumption. They also unmasked in the mdx heart: (i) compromised cardiac contractile function and efficiency, (ii) reduced cellular integrity, and (iii) exacerbated alterations in mitochondrial citric acid cycle-related parameters and in nutrient signaling pathways related to Akt. The observed shift in substrate selection cannot be explained by metabolic gene remodeling. However, mdx mice hearts showed an increased expression of the atrial natriuretic factor (anf) gene, an activator of the nitric oxide (NO)/cGMP signaling pathway and marker of cardiac remodeling, and, only as the cardiomyopathy progresses (at 25 weeks of age), an increased expression of the alpha1 subunit of soluble guanylate cyclase, which is known to negatively correlate with the activity NO/cGMP pathway. Collectively, our results highlight early metabolic and signaling alterations in the dystrophin-deficient heart, which may predispose these hearts to contractile dysfunction and sarcolemmal fragility. They also suggest the presence of a "sub-clinical" defect in the NO/cGMP pathway, which in vivo, at an early age, may be compensated by enhanced anf gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-29
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17583724-Animals, pubmed-meshheading:17583724-Carbohydrate Metabolism, pubmed-meshheading:17583724-Cardiomyopathies, pubmed-meshheading:17583724-Citrates, pubmed-meshheading:17583724-Citric Acid Cycle, pubmed-meshheading:17583724-Cyclic GMP, pubmed-meshheading:17583724-Dystrophin, pubmed-meshheading:17583724-Fatty Acids, pubmed-meshheading:17583724-Gene Expression Regulation, pubmed-meshheading:17583724-L-Lactate Dehydrogenase, pubmed-meshheading:17583724-Male, pubmed-meshheading:17583724-Mice, pubmed-meshheading:17583724-Mice, Inbred C57BL, pubmed-meshheading:17583724-Mice, Inbred mdx, pubmed-meshheading:17583724-Myocardium, pubmed-meshheading:17583724-Nitric Oxide, pubmed-meshheading:17583724-Phosphorylation, pubmed-meshheading:17583724-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17583724-Pyruvates, pubmed-meshheading:17583724-RNA, Messenger, pubmed-meshheading:17583724-Signal Transduction, pubmed-meshheading:17583724-Substrate Specificity, pubmed-meshheading:17583724-Ventricular Function, Left
pubmed:year
2007
pubmed:articleTitle
Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy.
pubmed:affiliation
Montreal Heart Institute and University of Montreal, 5000 Belanger St., Montreal, Quebec, Canada H1T 1C8.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural