Abstract:
OBJECTIVE:We have previously shown that cardiac-directed expression of adenylycyclase type VI (AC(VI)) increases heart function in transgenic mice, and improves heart function and survival in murine cardiomyopathy. However, a potential problem of crossbreeding paradigms that use lines with two constitutively active transgenes is that results can be obfuscated by interactions between transgenes during growth and development. METHODS:To develop a model that could be used subsequently to address this generic problem, transgenic mice with tetracycline (tet)-regulated cardiac-specific expression of AC(VI) were generated. In this transgenic strain, the expression of a tet-controlled transactivator (tTA) was under control of the rat alpha-myosin heavy chain promoter. Expression of the AC(VI) gene was driven by a tet-response element (TRE) and a minimal CMV promoter. RESULTS:Homogenates of hearts showed no change in AC(VI) protein content during tet suppression (doxycycline), confirming successful suppression of transgene expression. Removal of tet suppression for 10 days was associated with a 10-fold increase in cardiac AC(VI) protein content. A similar increase in mRNA was observed (Northern blot analysis). The estimated half-life of newly synthesized cardiac AC(VI) protein was 2-3 days. Isolated cardiac myocytes from animals that had tet-suppression removed for 10 days showed increased cAMP production in response to forskolin stimulation (Transgene Off: 15+/-6 fmol/microg; Transgene On: 39+/-14 fmol/microg; n=5 each group; P=0.004) and also to isoproterenol stimulation (Transgene Off: 20+/-5 fmol/microg; Transgene On: 31+/-12 fmol/microg; n=5 each group; P=0.035) and hearts isolated from these animals showed marked increased left ventricular peak dP/dt in response to dobutamine stimulation (P=0.009) indicating that inducible cardiac AC(VI) is functionally coupled and recruitable. CONCLUSION:We have generated transgenic mice with controlled cardiac-specific expression of AC(VI), provided detailed information regarding the kinetics of transgene expression and suppression and estimated the half-life of cardiac AC(VI) protein to be 2-3 days. Finally, we have shown, for the first time, that controlled cardiac-directed expression of a transgene can increase cardiac myocyte cAMP generation and left ventricular contractile function.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Gao MH,Bayat H,Roth DM,Yao Zhou J,Drumm J,Burhan J,Hammond HKdoi
10.1016/s0008-6363(02)00539-4subject
Has Abstractpub_date
2002-11-01 00:00:00pages
197-204issue
2eissn
0008-6363issn
1755-3245pii
S0008636302005394journal_volume
56pub_type
杂志文章abstract::Activation of sphingosine kinase/sphingosine-1-phosphate (SK/S1P)-mediated signalling has been recognized as critical for cardioprotection in response to acute ischaemia/reperfusion injury. Incubation of S1P with cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischaemia or ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn309
更新日期:2009-05-01 00:00:00
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journal_title:Cardiovascular research
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doi:10.1093/cvr/cvaa070
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the possible role of prostacyclin (PGI2) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). METHODS:Measurement of mRNA and protein levels of PGH synthase (PGHS)-1, PGI2 synthase and the PGI2 receptor, in the thoracic aorta was performed in SHR...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00239-9
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVES:Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.11.001
更新日期:2007-02-01 00:00:00
abstract:AIMS:The role of endothelial nitric oxide synthase (eNOS)/NO signalling is well documented in late ischaemic preconditioning (IPC); however, the role of eNOS and its activation in early IPC remains controversial. This study investigates the role of eNOS in early IPC and the signalling pathways and molecular interaction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs287
更新日期:2013-01-01 00:00:00
abstract::The effect of axial rotation on flow through and pressure gradient across saphenous vein segments was studied using 15 cadaver long saphenous veins. A significant reduction in flow occurred at a mean rotation of 25 degrees/cm and a significant increase in head loss across the segments occurred at a mean rotation of 23...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.4.538
更新日期:1975-07-01 00:00:00
abstract::Protein kinase A (PKA) is a central regulator of cardiac performance and morphology. Myocardial PKA activation is induced by a variety of hormones, neurotransmitters and stress signals, most notably catecholamines secreted by the sympathetic nervous system. Catecholamines bind β-adrenergic receptors to stimulate cAMP-...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvab008
更新日期:2021-01-23 00:00:00
abstract::Changes in left ventricular internal diameter resulting from increasing intrapericardial pressure induced by increasing the pericardial fluid volume were studied in closed chest, anaesthetized dogs. Left ventricular internal diameters were measured by placing an ultrasonic dimension catheter in the left ventricle at t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.6.707
更新日期:1975-11-01 00:00:00
abstract:AIMS:Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:Mice ...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt235
更新日期:2014-01-01 00:00:00
abstract::Atherosclerosis is characterized by a persistent, low-grade inflammation of the arterial wall. Monocytes and monocyte-derived macrophages play a pivotal role in the various stages of atherosclerosis. In the past few years, metabolic reprogramming has been identified as an important controller of myeloid cell activatio...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz107
更新日期:2019-07-01 00:00:00
abstract:OBJECTIVE:Determine if ischemic tolerance is reduced in the setting of experimental heart failure (HF). METHODS:Dogs were paced for 3 weeks at 240 BPM to induce heart failure which was confirmed with hemodynamic and echocardiographic measurements. The pacemaker was turned off 30 min prior to the ischemia study. Normal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00028-4
更新日期:1996-08-01 00:00:00
abstract:AIMS:The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined. METHODS AND RESULTS:Whole-cell patch-clamp recordings showed outward-rectifying currents in hum...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp153
更新日期:2009-08-01 00:00:00
abstract::The velocity of contraction has been reported to be more rapid in left atrium (LA) than left ventricle (LV), but the mechanics of contraction in these two chambers have not been compared under physiological conditions. Accordingly, sonomicrometer crystals and solid state pressure transducers were used to measure LV an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.10.604
更新日期:1984-10-01 00:00:00
abstract:OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00036-4
更新日期:1998-06-01 00:00:00
abstract:AIMS:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcriptional regulators. PPARdelta has an established role in metabolism, wound healing, and angiogenesis. However, little is known about its function in endothelial homeostasis. We investigat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp365
更新日期:2010-03-01 00:00:00
abstract::This study is the first report describing the sequence of biochemical alterations of myocardium during the progression of naturally occurring hypertrophy in spontaneously hypertensive rats (SHRs) and then with its reversal by alpha-methyldopa therapy. Changes in DNA, RNA, hydroxyproline, as well as incorporation of 14...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.2.254
更新日期:1976-03-01 00:00:00
abstract::Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking u...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.6.352
更新日期:1980-06-01 00:00:00
abstract:BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00320-5
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVE:The aim was to test the hypothesis that nitric oxide (or a related compound) contributes to the coronary vasodilatation during physiological increases of myocardial O2 consumption that occur with exercise. METHODS:Active hyperaemia associated with graded treadmill exercise and coronary reactive hyperaemia we...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.1.119
更新日期:1994-01-01 00:00:00
abstract:AIMS:Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS:Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naï...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz102
更新日期:2020-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00191-6
更新日期:1998-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00710-1
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:A circadian rhythm of blood pressure has been demonstrated both in subjects who are physically active during the day and in those confined to bed. The study of the circadian rhythm of arterial flow and peripheral resistance, on the other hand, is limited to pioneer experiments. This paper is aimed at demonstr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00237-5
更新日期:1999-01-01 00:00:00
abstract:OBJECTIVE:Activin-like kinase receptor 1 (ALK1) is a transforming growth factor (TGF)-beta type I receptor expressed in vascular mesenchyme, yet its function in vascular mesenchymal cells (VMC) is unclear. We examined ALK1 expression in human coronary atherosclerotic lesions and bovine and human VMC undergoing cellular...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.09.014
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:Increased pulse pressure has been observed in aging subjects, but the impact on the structure and reactivity of small arteries has been scarcely evaluated. METHODS:This study presents the modifications of vascular structure and function observed in female rats of 5, 18 and 32 months of age, and their relatio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00225-3
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS:Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the follo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00455-8
更新日期:2002-08-15 00:00:00
abstract:OBJECTIVE:The aim was to investigate whether intrinsic cardiac neurones can be involved in the genesis of ventricular arrhythmias. METHODS:Nicotinic, muscarinic, beta adrenergic, peptidergic, and amino acidergic agonists, as well as purinergic compounds, were individually administered in microliter quantities adjacent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.5.636
更新日期:1994-05-01 00:00:00
abstract::The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved an...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00293-9
更新日期:1998-03-01 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:Left ventricular assist devices (LVAD) have been used to 'bridge' patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called 'reverse remodeling', the underlying biological mecha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00433-3
更新日期:2002-01-01 00:00:00