Abstract:
OBJECTIVE:Neointimal hyperplasia is a central feature in the pathogenesis of a variety of vascular pathologies. Mitogen-activated protein kinases (MAPK) are involved in the downstream transduction of signals from receptors for many of the molecules known to be instrumental in this process and thus represent a potential target for the modification of the proliferative response. We examined the hypothesis that down-regulation of MAPK would inhibit neointima formation in a porcine coronary injury model. METHODS:Balloon angioplasty was performed on 38 coronary arteries from 23 large white pigs. Antisense oligonucleotides to the p42 and p44 MAPK were locally delivered to the site of injury immediately after balloon injury. At 7 or 21 days, arteries were harvested for morphometry, determination of cell proliferation and assessment of MAPK protein levels. RESULTS:At 7 days, neointima formation was significantly reduced compared to controls (corrected intima/media ratio (IMR) 1.01+/-0.13 vs. 1.61+/-0.07, P<0.01) and this was associated with a 58% and 23% down-regulation of p42 and p44 protein levels, respectively. Intimal and medial proliferation rates were also reduced by 32% and 26%, respectively. At 21 days however, the effect of the treatment on MAPK protein levels was no longer significant and this correlated with a loss of the effects on IMR and cell proliferation. CONCLUSIONS:Down-regulation of MAPK inhibits early smooth muscle cell (SMC) proliferation and neointimal thickening in response to arterial injury, implying that it plays an important role in determining the early vascular response to injury. Inhibitory effects were less apparent at 21 days after a single delivery of oligonucleotide, implying that more sustained local delivery may be required to achieve longer term therapeutic benefit.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Liu B,Fisher M,Groves Pdoi
10.1016/s0008-6363(02)00335-8subject
Has Abstractpub_date
2002-06-01 00:00:00pages
640-8issue
3eissn
0008-6363issn
1755-3245pii
S0008636302003358journal_volume
54pub_type
杂志文章abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.021
更新日期:2007-11-01 00:00:00
abstract:Aims:Dilated cardiomyopathy (DCM) induced chronic heart failure is a life-threatening disease worldwide. Long non-coding RNAs (lncRNAs) are potential new therapeutic targets and may provide new pathophysiological mechanisms for development of DCM. Methods and results:Microarray assays in 14 DCM and 10 control human he...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy012
更新日期:2018-04-01 00:00:00
abstract:STUDY OBJECTIVE:It has been suggested that oxygenation of the isolated, crystalloid perfused, Langendorff rabbit heart is inadequate and that consequent hypoxia limits mechanical performance. The isolated working rabbit heart, which has a higher oxygen requirement than the Langendorff preparation, was used to investiga...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.3.198
更新日期:1991-03-01 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:AIMS:Brugada syndrome (BrS) is an autosomal-inherited cardiac arrhythmia characterized by an ST-segment elevation in the right precordial leads of the electrocardiogram and an increased risk of syncope and sudden death. SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS. Despite the f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs211
更新日期:2012-10-01 00:00:00
abstract:AIM:The aim of the study was to determine the potential for K(V)1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. METHODS AND RESULTS:Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptase-polymerase chain reaction and immunocytochemistry were used to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq305
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:The vasoconstrictor effect of endothelins (ET) is mediated by endothelin A (ETA) and endothelin B (ETB) receptors. Furthermore, ETB receptor stimulation results in release of vasodilators. Hence, ETA receptor antagonists should attenuate ET-mediated vasoconstriction. The aim of the present study was to evalua...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00152-7
更新日期:1998-09-01 00:00:00
abstract::The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed. The techniques for data acqusition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.4.277
更新日期:1977-07-01 00:00:00
abstract:AIMS:TGF-β regulates tissue fibrosis: TGF-β promotes fibrosis, whereas bone morphogenetic protein (BMP)-7 is antifibrotic. To demonstrate that (i) left ventricular (LV) remodelling after pressure overload is associated with disequilibrium in the signalling mediated by these cytokines, and (ii) BMP-7 exerts beneficial e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw076
更新日期:2016-06-01 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:To study the intracellular pathways which mediate the inhibitory actions of adenosine on isoprenaline-stimulated calcium current (ICa) in atrioventricular (AV) nodal myocytes. METHODS:The whole-cell patch-clamp technique was used to record ICa from rabbit AV nodal cells, isolated by enzymatic and mechanical ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00043-6
更新日期:1997-05-01 00:00:00
abstract:AIMS:The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may c...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu152
更新日期:2014-09-01 00:00:00
abstract:AIMS:Despite their ability to cause septic shock and myocardial dysfunction, components of Gram-negative bacterial cell walls, like lipopolysaccharide, have been shown in numerous studies to induce myocardial protection during ischaemia-reperfusion injury. Muramyl dipeptide (MDP) is another such component recognized by...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp055
更新日期:2009-07-15 00:00:00
abstract::Sprouting angiogenesis is an invasive process that involves proteolytic activities required for the degradation of the endothelial basement membrane, cell migration with removal of obstructing matrix proteins, and generation of space in the matrix to allow endothelial cells to form a proper lumen. In the last decade i...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm102
更新日期:2008-05-01 00:00:00
abstract:AIMS:KCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K(+) channel responsible for I(Ks)-a major repolarizing current in the human heart-and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn085
更新日期:2008-08-01 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:AIMS:Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this A...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn350
更新日期:2009-03-01 00:00:00
abstract:AIMS:AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown to inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK β1/β2 subunits (AMPKβ1β2-deficient mice, β1β2M-KO) have been generated and possess <10% of...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv166
更新日期:2015-07-15 00:00:00
abstract:OBJECTIVE:Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents. METHODS:In phenobarbital-anaesthetised rats hypotension was induced b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00194-7
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVES:Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ETA and ETB receptor su...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00266-0
更新日期:1997-03-01 00:00:00
abstract::Pressure--diameter loops were generated in normal, conscious dogs during left ventricular contraction by means of endocardial ultrasonic gauges and micromanometers. Studies were made in the control state, during volume and pressure loading, and during enhancement of contractility. The diameter at the end of ejection w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.4.447
更新日期:1975-07-01 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:OBJECTIVE:To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes. METHODS:iNOS expression was studied in isolated neonatal rat ventricular myocyte cultures in response to bacterial lipopolysaccharide (LPS) or ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.05.026
更新日期:2006-09-01 00:00:00
abstract::The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology beh...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00025-0
更新日期:2000-06-01 00:00:00
abstract:Aims:Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy077
更新日期:2018-07-01 00:00:00
abstract:STUDY OBJECTIVE:Compensatory mechanisms of the left ventricle for volume overloading caused by acute aortic regurgitation and associated changes in physiological properties of the aorta were studied in rabbits. DESIGN:Aortic regurgitation was produced by aortic valve perforation, and haemodynamic measurements were per...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.6.463
更新日期:1991-06-01 00:00:00
abstract::The second messenger cyclic guanosine 3'5' monophosphate (cGMP) and its downstream effector protein kinase G (PKG) have been discovered more than 40 years ago. In vessels, PKG1 induces smooth muscle relaxation in response to nitric oxide signalling and thus lowers systemic and pulmonary blood pressure. In platelets, P...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw107
更新日期:2016-07-15 00:00:00
abstract:OBJECTIVE:Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.07.004
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:While natriuretic peptides can inhibit growth of vascular muscle cells (VSMC), controversy exists as to whether this effect is mediated via the guanylate cyclase-coupled receptors, NPR-A and NPR-B, or the clearance receptor, NPR-C. The original aim of this study was to examine the mechanism by which the NPR-C...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00086-2
更新日期:1997-07-01 00:00:00
abstract::The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The ma...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.04.005
更新日期:2005-08-15 00:00:00