Abstract:
:cAMP-dependent protein kinase is anchored to discrete cellular compartments by a family of proteins, the A-kinase anchor proteins (AKAPs). We have investigated in vivo and in vitro the biological effects of the expression of a prototypic member of the family, AKAP75, on smooth muscle cells. In vitro expression of AKAP75 in smooth muscle cells stimulated cAMP-induced transcription, increased the levels of the cyclin-dependent kinase-2 inhibitor p27(kip1), and reduced cell proliferation. In vivo expression of exogenous AKAP75 in common carotid arteries, subjected to balloon injury, significantly increased the levels of p27(kip1) and inhibited neointimal hyperplasia. Both the effects in smooth muscle cells in vitro and in carotid arteries in vivo were specifically dependent on the amplification of cAMP-dependent protein kinase (PKA) signals by membrane-bound PKA, as indicated by selective loss of the AKAP75 biological effects in mutants defective in the PKA anchor domain or by suppression of AKAP effects by the PKA-specific protein kinase inhibitor. These data indicate that AKAP proteins selectively amplify cAMP-PKA signaling in vitro and in vivo and suggest a possible target for the inhibition of the neointimal hyperplasia after vascular injury.
journal_name
Circ Resjournal_title
Circulation researchauthors
Indolfi C,Stabile E,Coppola C,Gallo A,Perrino C,Allevato G,Cavuto L,Torella D,Di Lorenzo E,Troncone G,Feliciello A,Avvedimento E,Chiariello Mdoi
10.1161/01.res.88.3.319subject
Has Abstractpub_date
2001-02-16 00:00:00pages
319-24issue
3eissn
0009-7330issn
1524-4571journal_volume
88pub_type
杂志文章abstract:RATIONALE:Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. OBJECTIVE:To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306838
更新日期:2015-09-25 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.RES.0000155964.34150.F7
更新日期:2005-02-18 00:00:00
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更新日期:2012-06-22 00:00:00
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journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.111.255950
更新日期:2012-02-17 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2004-04-16 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.2.233
更新日期:2000-02-04 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304164
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
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更新日期:2006-12-08 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1975-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.69.5.1316
更新日期:1991-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2014-02-28 00:00:00
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pub_type: 杂志文章
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更新日期:1988-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000076891.24317.CA
更新日期:2003-06-13 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.44.2.161
更新日期:1979-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.5.728
更新日期:1985-05-01 00:00:00
abstract:RATIONALE:Increased sympathetic nerve activity has been linked to the pathogenesis of hypertension in humans and animal models. Enhanced peripheral chemoreceptor sensitivity which increases sympathetic nerve activity has been observed in established hypertension but has not been identified as a possible mechanism for i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206946
更新日期:2010-02-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206581
更新日期:2009-11-06 00:00:00
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pub_type: 杂志文章
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更新日期:2003-11-14 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1984-09-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.3.596
更新日期:1993-09-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.2.319
更新日期:1991-02-01 00:00:00
abstract:RATIONALE:Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated. OBJECTIVE:We studied the molecular mechanism mediating the effect of GSK-3β acti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.249532
更新日期:2011-08-19 00:00:00
abstract::Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. These studies have revealed...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.161778
更新日期:2008-02-29 00:00:00
abstract::The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.582
更新日期:1991-09-01 00:00:00
abstract::Physiological or pathological stresses and strains produce longer or wider muscle cells, but resting sarcomere length remains constant. Our goal was to investigate the cellular mechanisms for controlling this optimal, resting sarcomere length. To do so, we cultured neonatal rat cardiomyocytes on microfabricated peg-an...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2004-03-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.1.218
更新日期:1990-01-01 00:00:00
abstract::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.9.768
更新日期:2000-10-27 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.6.1059
更新日期:1988-06-01 00:00:00