Abstract：
AIMS:Cardiac β-adrenergic receptors (β-AR) are key regulators of cardiac haemodynamics and size. The scaffolding protein A-kinase anchoring protein 79/150 (AKAP5) is a key regulator of myocardial signalling by β-ARs. We examined the function of AKAP5 in regulating cardiac haemodynamics and size, and the role of β-ARs and Ca(2+)-regulated intracellular signalling pathways in this phenomenon. METHODS AND RESULTS:We used echocardiographic, histological, genetic, and biochemical methods to examine the effect of ablation of AKAP5 on cardiac haemodynamics, size, and signalling in mice. AKAP5(-/-) mice exhibited enhanced signs of cardiac dilatation and dysfunction that progressed with age. Infusions of isoprenaline worsened cardiac haemodynamics in wild-type (WT) mice only, but increased the ratio of heart-to-body weight equally in WT and in AKAP5(-/-) mice. Mechanistically, loss of AKAP5 was associated with enhanced activity of cardiac calmodulin kinase II (CaMKII) and calcineurin (CaN) as indexed by nuclear factor of activated T-cell-luciferase activity. Loss of AKAP5 interfered with the recycling of cardiac β1-ARs, which was mediated in part by CaN binding to AKAP5. Carvedilol reversed cardiac hypertrophy and haemodynamic deficiencies in AKAP5(-/-) mice by normalizing the activities of cardiac CaN and CaMKII. CONCLUSIONS:These findings identify a novel cardioprotective role for AKAP5 that is mediated by regulating the activities of cardiac CaN and CaMKII and highlight a significant role for cardiac β-ARs in this phenomenon.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Li X,Matta SM,Sullivan RD,Bahouth SWdoi
10.1093/cvr/cvu209subject
Has Abstractpub_date
2014-11-01 00:00:00pages
270-9issue
2eissn
0008-6363issn
1755-3245pii
cvu209journal_volume
104pub_type
杂志文章abstract：AIMS:Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine. Although it has been used for thousands of years to treat stroke, the mechanisms of action of S. baicalensis have not been clearly elucidated. In this report, we studied the modulation of angi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvq296
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journal_title：Cardiovascular research
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvx133
更新日期：2017-09-01 00:00:00
abstract：AIMS :Activation of the angiotensin (Ang)-(1-7)/Mas receptor (R) axis protects from sympathetic overactivity. Endocytic trafficking is an essential process that regulates receptor (R) function and its ultimate cellular responses. We investigated whether the blunted responses to Ang-(1-7) in hypertensive rats are associ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz332
更新日期：2020-10-01 00:00:00
abstract：:Twenty patients who had suffered myocardial infarction within the previous 3 to 13 days performed face immersion with breath-holding. The maximum reduction in heart rate was 17 +/- 9 beats-min--1 (mean +/- SD). When compared with 24 patients without evidence ischaemic heart disease, they behaved more like younger pati...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/12.4.239
更新日期：1978-04-01 00:00:00
abstract：AIMS:Adverse cardiovascular events in humans occur with a day/night pattern, presumably related to a daily pattern of behaviours or endogenous circadian rhythms in cardiovascular variables. Healthy humans possess a scale-invariant/fractal structure in heartbeat fluctuations that exhibits an endogenous circadian rhythm ...
journal_title：Cardiovascular research
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doi：10.1093/cvr/cvn150
更新日期：2008-10-01 00:00:00
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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
abstract：:Sinoatrial conduction times, estimated by premature atrial stimulation, were compared with direct measurement of the sinoatrial conduction time in 15 isolated rabbit sinus node preparations before and after intrasinusal pacemaker shifts induced by cooling. Transmembrane potentials and surface electrograms were recorde...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/20.2.81
更新日期：1986-02-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00335-8
更新日期：2002-06-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/0008-6363(95)00235-9
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/24.9.754
更新日期：1990-09-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/27.9.1555
更新日期：1993-09-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.11.010
更新日期：2007-02-01 00:00:00
abstract：OBJECTIVE:Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted f...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.09.015
更新日期：2006-01-01 00:00:00
abstract：:We studied the effects of intracoronary vasopressin on the relationship between pressure and flow in the coronary circulation of anaesthetised swine. In addition to measurements at control levels, diastolic pressure-flow relationships were constructed from steady-state points below a coronary pressure of 50 mmHg, wher...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/19.7.433
更新日期：1985-07-01 00:00:00
abstract：:The effect of acetylcholine on the aconitine induced delayed afterdepolarisation and triggered electrical activities under nominally calcium free conditions were studied in frog atrium and ventricle. The changes in intracellular potassium activity were also examined. The aconitine induced delayed afterdepolarisation a...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/21.11.804
更新日期：1987-11-01 00:00:00
abstract：AIMS:Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating h...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz118
更新日期：2019-11-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvv204
更新日期：2015-10-01 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：10.1016/s0008-6363(02)00657-0
更新日期：2003-01-01 00:00:00
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journal_title：Cardiovascular research
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doi：10.1093/cvr/13.10.578
更新日期：1979-10-01 00:00:00
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journal_title：Cardiovascular research
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更新日期：2018-03-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.10.869
更新日期：1991-10-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz145
更新日期：2020-03-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(99)00008-5
更新日期：1999-06-01 00:00:00
abstract：:Experimental studies have provided evidence that the autonomic nervous activity is modulated by oestrogen. Such modulation at central and peripheral levels tends to suppress sympathetic but elevate parasympathetic tone to the cardiovascular system. Thus, available data support the view that cardiovascular protection b...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：
更新日期：1995-08-01 00:00:00
abstract：OBJECTIVE:Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the underlying mechanisms are still unknown. In this study, we investigated in isolated rat cardiomyocytes subjected to hypoxia and reoxygenation whether administration of insulin during reo...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.02.020
更新日期：2006-05-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvaa285
更新日期：2020-10-16 00:00:00
abstract：:Diabetes is one of the most prevalent chronic conditions that has a high association with death from cardiovascular disease(s). An impaired cardiac function independent of vascular disease suggests the existence of a primary myocardial defect in diabetes mellitus. We and others have documented that myocardial performa...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/s0008-6363(97)00059-x
更新日期：1997-04-01 00:00:00
abstract：AIMS:Vascular endothelial growth factor-C (VEGF-C) has been shown to stimulate both angiogenesis and lymphangiogenesis in some but not all models where VEGF-C is over-expressed. Our aim was to investigate the interaction between lymphangiogenesis and angiogenesis in adult tissues regulated by VEGF-C and identify eviden...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvm094
更新日期：2008-05-01 00:00:00
