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 interactions that regulate eNOS activation during early IPC. METHODS AND RESULTS:Rat hearts were subjected to 30-min global ischaemia and reperfusion (I/R) with or without IPC (three cycles 5-min I and 5-min R) in the presence or absence of the NOS inhibitor l-NAME, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY), and protein kinase A (PKA) inhibitor H89 during IPC induction or prior endothelial permeablization. IPC improved post-ischaemic contractile function and reduced infarction compared with I/R with this being abrogated by l-NAME or endothelial permeablization. eNOS(Ser1176), Akt(Ser473), and PKA(Thr197) phosphorylation was increased following IPC. I/R decreased eNOS(Ser1176) phosphorylation, whereas IPC increased it. Mass spectroscopy confirmed eNOS(Ser1176) phosphorylation and quantitative Western blots showed ∼24% modification of eNOS(Ser1176) following IPC. Immunoprecipitation demonstrated eNOS, Akt, and PKA complexation. Immunohistology showed IPC-induced Akt and PKA phosphorylation in cardiomyocytes and endothelium. With eNOS activation, IPC increased NO production as measured by electron paramagnetic resonance spin trapping and fluorescence microscopy. LY or H89 not only decreased Akt(Ser473) or PKA(Thr197) phosphorylation, respectively, but also abolished IPC-induced preservation of eNOS and eNOS(Ser1176) phosphorylation as well as cardioprotection. CONCLUSION:Thus, Akt- and PKA-mediated eNOS activation, with phosphorylation near the C-terminus, is critical for early IPC-induced cardioprotection, with eNOS-derived NO from the endothelium serving a critical role.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Yang C,Talukder MA,Varadharaj S,Velayutham M,Zweier JLdoi
10.1093/cvr/cvs287subject
Has Abstractpub_date
2013-01-01 00:00:00pages
33-43issue
1eissn
0008-6363issn
1755-3245pii
cvs287journal_volume
97pub_type
杂志文章abstract::To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkalo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.8.514
更新日期:1984-08-01 00:00:00
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
abstract::The cardiospecificity of the MB isoenzyme of creatine kinase, EC 2.7.3.2, (CK) with its associated diagnostic and research value has resulted in the development of a number of procedures for the separation and quantitation of the three isoenzymes of CK. In our experience methods involving cellulose acetate electrophor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.94
更新日期:1977-03-01 00:00:00
abstract:CONDENSED ABSTRACT:We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00164-3
更新日期:1998-12-01 00:00:00
abstract:AIMS:Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt067
更新日期:2013-06-01 00:00:00
abstract:AIMS:We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients. METHODS AND RESULTS:ApoE(-/-)RAG2(-/-) mice received four intravenous injections of sa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm034
更新日期:2008-02-01 00:00:00
abstract:AIMS:The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via in...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu184
更新日期:2014-10-01 00:00:00
abstract::Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechani...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00367-4
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVE:We recently showed that mitochondrial coupling factor 6 (CF6) is present as a pressor substance and a prostacyclin inhibitor in systemic circulation. However, the regulation mechanism for circulating CF6 is unknown. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the generation and rele...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.01.031
更新日期:2004-06-01 00:00:00
abstract::There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.740
更新日期:1986-10-01 00:00:00
abstract:OBJECTIVE:This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist. METHODS:ApoE-deficient and C57BL/6J control mice...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00469-2
更新日期:2002-02-01 00:00:00
abstract:AIMS:Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz136
更新日期:2019-12-01 00:00:00
abstract::Inherited arrhythmias are disorders caused by one or more genetic mutations that increase the risk of arrhythmia, which result in life-long risk of sudden death. These mutations either primarily perturb electrophysiological homeostasis (e.g. long QT syndrome and catecholaminergic polymorphic ventricular tachycardia), ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa107
更新日期:2020-07-15 00:00:00
abstract:AIMS:17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not ful...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs281
更新日期:2012-12-01 00:00:00
abstract::A pulsed, range gated, directional, ultrasonic, Doppler blood velocity meter was used to record signals from the pulmonary artery in 52 normal subjects ranging in age from less than 1 week to over 30 years. Signals were obtained from an unfocused transducer in the second or third left intercostal space using a 2.25 MH...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.11.816
更新日期:1986-11-01 00:00:00
abstract:AIMS:Hyperhomocysteinaemia is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial dysfunction. Homocysteine modulates cellular methylation reactions. P66shc is a protein that promotes oxidative stress whose expression is governed by promoter methylation. We asked ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr250
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.001
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:The aim of the presented method was the characterization of different complex heart rate dynamics in conscious rabbits as well as during general anaesthesia and vagal blockade. This was done by non-linear prediction of original measured and special surrogate data in the phase space. METHOD:The development of...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::An in situ preparation of the rabbit thoracic aorta has been used to study the transport of short-lived radioactive isotopes of oxygen (15O16O), nitrogen (13N14N) and an isotope of xenon (133Xe) from 0.9% NaCl into the artery wall. At a luminal hydrostatic pressure of 2 kPa the uptake of all three isotopes by the inti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.8.456
更新日期:1981-08-01 00:00:00
abstract:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00144-3
更新日期:1999-09-01 00:00:00
abstract:AIMS:GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs001
更新日期:2012-03-15 00:00:00
abstract:OBJECTIVE:The aim was to evaluate the hypothesis that the oxygen demand of stimulated myocardium is downregulated and ischaemia avoided when oxygen supply is limited. METHODS:Isoprenaline stimulation during reduced coronary perfusion pressure or moderate coronary hypoxaemia was studied in relation to myocardial oxygen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.8.1542
更新日期:1993-08-01 00:00:00
abstract:OBJECTIVE:The present work is aimed at elucidating the signalling pathway(s) triggered by activation of A(2A) receptors involved in the facilitation of noradrenaline release in rat tail artery as an attempt to clarify their role in the cardiovascular system. METHODS:Electrically evoked (5 Hz, 100 pulses, 1 ms) tritium...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.05.015
更新日期:2004-09-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS:Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.9.839
更新日期:1992-09-01 00:00:00
abstract:AIMS:Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, promotes endothelial cell migration via stimulation of phosphoinositide 3-kinase (PI3K). The aim of this study was to identify the role of PI3Kbeta and gamma isoforms and their downstream effector pathways in mediating endothe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn159
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:The presence is well established in unstable angina of intracoronary thrombosis in a stenosed epicardial coronary artery. The effects of the thrombus formation on the distal microcirculation are however still unclear. METHODS:We adapted the Folts canine model of left circumflex coronary arterial stenosis and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00270-3
更新日期:1999-04-01 00:00:00
abstract::We tested the hypothesis that visualisation of defects on thallium-201 (201Tl) myocardial perfusion images (MPI) depends on the duration of the ischaemic state between 201Tl injection and the time of reperfusion of an occluded coronary artery. Praecordial imaging with a gamma camera was performed in 24 anaesthetised, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.1.47
更新日期:1982-01-01 00:00:00
abstract:AIMS:Percutaneous implantation has already been used clinically and is a great option for treating young patients. The use of autologous tissue-engineered valved stents might solve the problem of degeneration and limited durability of biological heart valves. METHODS AND RESULTS:Porcine pulmonary heart valves and smal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq212
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVES:While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed form...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract:AIMS:SR-B1 is a cholesterol transporter that exerts anti-atherogenic properties in liver and peripheral tissues in mice. Bone marrow (BM) transfer studies suggested an atheroprotective role in cells of haematopoietic origin. Here, we addressed the specific contribution of SR-B1 in the monocyte/macrophage. METHODS AND ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz138
更新日期:2020-03-01 00:00:00