Linked Life Data

11786048

Source:http://linkedlifedata.com/resource/pubmed/id/11786048

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-1-11
pubmed:abstractText
The spontaneously hypertensive heart failure (SHHF) rat shares numerous functional and molecular characteristics of human heart failure (HF), including impairment of beta-adrenergic receptor (AR) signaling with decreased betaAR density and coupling to adenylyl cyclase as well as increased betaAR kinase (betaARK1) levels and activity. We examined the effects of betaARK1 inhibition on the signaling and contractile function in failing ventricular myocytes isolated from SHHF rat hearts. This was done by adenoviral-mediated gene transfer of the carboxy-terminal 194 amino acids of betaARK1 (betaARKct), which acts as an in vivo betaARK1 inhibitor. Basal cAMP production was reduced in cells from SHHF rat hearts (n=4) compared with that found in cells isolated from the hearts of age-matched Sprague-Dawley (SD) control rats (n=8; SHHF, 2.5+/-0.2% conversion [(3)H]adenine to cAMP, versus SD, 4.2+/-0.2%; P<0.01), as were cAMP responses to the beta-agonist iso-proterenol (ISO; SHHF, 5.2+/-0.2%, versus SD, 7.2+/-0.4%; P<0.01). Following betaARKct expression, SHHF cardiomyocytes displayed a significant increase in basal (6.6+/-0.6%, P<0.01) and ISO-stimulated cAMP production (8.8+/-0.6%, P<0.01) versus failing myocytes treated with an empty adenovirus. Concerning contractile function of these cells, betaARKct expression produced significant improvement in ISO (10(-6) M) stimulated (n=7 hearts) cell shortening, relaxation, and contraction compared with failing cells treated with the control empty virus (betaARKct, 39+/-11%, 70+/-18%, and 70+/-20%, versus empty virus, 1+/-7%, 5+/-5%, and 0+/-7%, respectively). Thus, these data indicate that targeted betaARK1 inhibition via genetic manipulation is a powerful therapeutic approach for improving the function of failing cardiomyocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
74-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Expression of a beta-adrenergic receptor kinase inhibitor reverses dysfunction in failing cardiomyocytes.
pubmed:affiliation
Departments of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Comparative Study