Abstract:
OBJECTIVE:To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS:A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of transgenic mice. Upon confirming that a partial replacement of endogenous protein with transgenic protein occurred, the biochemical and physiological consequences were studied. PKA-dependent phosphorylation assays were used to estimate the phosphorylation states of major cardiac PKA substrates. Myofibril Mg-ATPase activities were also measured. Isolated working heart and whole animal exercise studies were used to measure the physiological changes. RESULTS:Transgenic mice displayed a compensatory response, with PKA-mediated phosphorylation of both troponin I and phospholamban showing significant increases. The remaining endogenous cardiac MyBP-C also showed increased phosphorylation levels. Maximal Mg(2+)-ATPase activity was increased. Significant functional changes at both the whole organ and whole animal levels also occurred. Parameters reflecting cardiac contractility and relaxation increased about 22 and 25%, respectively, in the mutant relative to wild type mice (n=5, P<0.001). In young adults the capacity for stress exercise, quantitated using an exercise treadmill regimen, was substantially enhanced (n=6, P<0.01). CONCLUSIONS:Cardiac MyBP-C phosphorylation plays an important physiological role and that the protein's degree of phosphorylation is coordinated with the phosphorylation levels of other proteins within the contractile apparatus.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Yang Q,Hewett TE,Klevitsky R,Sanbe A,Wang X,Robbins Jdoi
10.1016/s0008-6363(01)00273-5subject
Has Abstractpub_date
2001-07-01 00:00:00pages
80-8issue
1eissn
0008-6363issn
1755-3245pii
S0008636301002735journal_volume
51pub_type
杂志文章abstract:OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVES:To elucidate the effect of selective endothelin ET(A)- and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction (MI). METHODS:Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats 12 weeks afte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00083-3
更新日期:2000-07-01 00:00:00
abstract:AIMS:Smad7 plays a negative regulatory role in many inflammatory diseases, but its effect on hypertensive disease remains unknown. The present study tested the hypothesis that overexpression of Smad7 may have therapeutic potential for angiotensin II (Ang II)-mediated hypertensive cardiac remodelling. METHODS AND RESUL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt151
更新日期:2013-09-01 00:00:00
abstract:AIMS:Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. METHODS AND RESULT...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy257
更新日期:2019-03-15 00:00:00
abstract::The effect of digoxin, at two different inotropic levels, was examined in normo- and hyperkalaemic dogs. For similar inotropic responses, normo- and hyperkalaemic dogs had similar levels of (Na+, K+)-ATPase inhibition and microsomal-bound digoxin. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.4.515
更新日期:1975-07-01 00:00:00
abstract:AIMS:To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments. METHODS AND RESULTS:National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 pati...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvz197
更新日期:2020-01-01 00:00:00
abstract::Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.03.004
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS:Right atrial appendages were obtained from eight patients with paroxysmal AF, ten ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00045-0
更新日期:1999-05-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp265
更新日期:2010-01-01 00:00:00
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journal_title:Cardiovascular research
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doi:10.1093/cvr/cvt001
更新日期:2013-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv096
更新日期:2015-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/cvr/27.11.2005
更新日期:1993-11-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affect myocardial oxygen consumption. Although NOS3 is a constitutive protein, its levels of expression can be modi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00059-5
更新日期:1998-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00107-3
更新日期:2000-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00142-x
更新日期:1999-08-01 00:00:00
abstract:AIMS:Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (LmnaH222P/H222P). The ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt106
更新日期:2013-08-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN:Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.8.633
更新日期:1990-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt238
更新日期:2014-01-01 00:00:00
abstract::The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.570
更新日期:1985-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.2.80
更新日期:1981-02-01 00:00:00
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doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00136-9
更新日期:1998-11-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00156-3
更新日期:1996-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.003
更新日期:2005-08-15 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00156-9
更新日期:1997-10-01 00:00:00
abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt265
更新日期:2014-03-01 00:00:00
abstract::The contractile response to beta-adrenoceptor stimulation has been found to be reduced in single myocytes from failing human ventricle. A portion of that reduction was statistically related to the age of the patient. We have developed a method for obtaining viable contracting myocytes from small biopsies of human vent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract:AIM:Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm069
更新日期:2008-02-01 00:00:00