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 detect gene expression. Whole-cell patch-clamp, intracellular calcium measurement, cell migration assays, and organ culture were used to assess channel function. K(V)1.3 was unique among the K(V)1 channels in showing preserved and up-regulated expression when the vascular smooth muscle cells switched to the proliferating phenotype. There was strong expression in neointimal formations. Voltage-dependent potassium current in proliferating cells was sensitive to three different blockers of K(V)1.3 channels. Calcium entry was also inhibited. All three blockers reduced vascular smooth muscle cell migration and the effects were non-additive. One of the blockers (margatoxin) was highly potent, suppressing cell migration with an IC(50) of 85 pM. Two of the blockers were tested in organ-cultured human vein samples and both inhibited neointimal hyperplasia. CONCLUSION:K(V)1.3 potassium channels are functional in proliferating mouse and human vascular smooth muscle cells and have positive effects on cell migration. Blockers of the channels may be useful as inhibitors of neointimal hyperplasia and other unwanted vascular remodelling events.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Cheong A,Li J,Sukumar P,Kumar B,Zeng F,Riches K,Munsch C,Wood IC,Porter KE,Beech DJdoi
10.1093/cvr/cvq305subject
Has Abstractpub_date
2011-02-01 00:00:00pages
282-9issue
2eissn
0008-6363issn
1755-3245pii
cvq305journal_volume
89pub_type
杂志文章abstract:AIMS:Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. METHODS AND RESULTS:Echocardiography and pressure-volume conductance catheters were us...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn129
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVES:Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract:AIMS:Bone marrow (BM) progenitor cells may contribute to vascular remodelling. The present study aimed to investigate the contribution of BM-derived CXCR4(+) (a CXC chemokine receptor) and PDGFRbeta(+) (platelet-derived growth factor receptor beta) progenitor cells in hypoxia-induced muscularization of alveolar arterio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq147
更新日期:2010-09-01 00:00:00
abstract::Cell communication, an essential component of integrated physiological function in multicellular organisms, is mediated largely through informational molecules, such as hormones and neurotransmitters. After binding to specific receptors, these first messengers activate intracellular signaling cascades and, thereby, tr...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00521-1
更新日期:2002-05-01 00:00:00
abstract:AIMS:Cardiac hypertrophy is a risk factor independent of blood pressure; however, the mechanisms that distinguish pathological remodelling due to local cues from pressure overload are unresolved. This study was aimed at discovering a novel gene expression mechanism in heart failure. METHODS AND RESULTS:In angiotensin ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp285
更新日期:2010-01-01 00:00:00
abstract:AIMS:TRPM2 is a Ca(2+)-permeable cationic channel of the transient receptor potential (TRP) superfamily that is linked to apoptotic signalling. Its involvement in cardiac pathophysiology is unknown. The aim of this study was to determine whether the pro-apoptotic cytokine tumour necrosis factor-α (TNF-α) induces a TRPM...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu112
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. METHODS...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00536-4
更新日期:2003-11-01 00:00:00
abstract:AIMS:Heart failure is associated with deficient endothelial nitric oxide (NO) production as well as increased oxidative stress and accelerated NO degradation. The aim of this study was to evaluate platelet NO biosynthesis and superoxide anion (O(2)(-)) production in patients with heart failure. METHODS AND RESULTS:In ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr115
更新日期:2011-09-01 00:00:00
abstract::Netrins are a family of laminin-like proteins, which were initially identified for their role in embryonic axonal guidance. Over recent years, it has become apparent that netrin-1 may additionally be involved in the underlying pathology of several multisystem diseases, making it an attractive potential therapeutic tar...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv201
更新日期:2015-09-01 00:00:00
abstract:OBJECTIVE:Previous studies showed that treatment of hearts with nisoldipine improves recovery of cardiac function following ischaemia, improves reperfusion, and reduces the constrictor sensitivity to endothelin. The aim of the present study was to assess the reduction in vasodilator responses that occurs following isch...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.990
更新日期:1993-06-01 00:00:00
abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00538-2
更新日期:2002-11-01 00:00:00
abstract:AIMS:JNJ-64179375 (hereafter JNJ-9375) is a first-in-class, highly specific, large molecule, exosite 1 thrombin inhibitor. In preclinical studies, JNJ-9375 demonstrated robust antithrombotic protection with a wider therapeutic index when compared to apixaban. The purpose of the present study was to examine for the firs...
journal_title:Cardiovascular research
pub_type: 杂志文章,随机对照试验
doi:10.1093/cvr/cvy227
更新日期:2019-03-01 00:00:00
abstract:AIMS:Proliferation of mammalian cardiomyocytes stops during the first weeks after birth, preventing the heart from regenerating after injury. Recently, several studies have indicated that induction of cardiomyocyte proliferation can be utilized to regenerate the mammalian heart. Thus, it is important to identify novel ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp360
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVE:Rapid ventricular pacing reliably induces severe congestive heart failure in dogs, with an associated attenuation of baroreflex sensitivity. Unique to this model is the capacity for rapid recovery of haemodynamics and plasma noradrenaline following the cessation of pacing; however, whether baroreflex sensitiv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.384
更新日期:1994-03-01 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:OBJECTIVE:We have previously demonstrated that nuclear factor kappa B (NFkappaB) activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.025
更新日期:2005-11-01 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::To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.4.294
更新日期:1986-04-01 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:Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.10.019
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:The aim was to estimate the relative contributions of the various intracellular and sarcolemmal systems to the relaxation of the systolic calcium transient. METHODS:The experiments were performed on isolated rat ventricular myocytes. The cells were loaded with the fluorescent indicator indo-1 in order to mea...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1826
更新日期:1993-10-01 00:00:00
abstract::Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic car...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz162
更新日期:2019-12-01 00:00:00
abstract::This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts during the second half of the 20th century at a period where pressure measurements were the rule. Thinking flow instead of pressure dynamics corresponded to in-depth conceptual changes: whereas blood pressure generally has a single posit...
journal_title:Cardiovascular research
pub_type: 社论,历史文章
doi:10.1016/s0008-6363(01)00307-8
更新日期:2001-08-01 00:00:00
abstract:OBJECTIVE:We tested the hypothesis that simultaneous inhibition of the endothelial integrin alpha(v)beta(3) and the platelet glycoprotein IIb/IIIa receptor will substantially reduce infarct size in a model of acute coronary thrombosis and primary angioplasty. METHODS:Dogs were subjected to thrombus formation in the le...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.01.016
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:Impairment of endothelium-dependent relaxation is related to dyslipidemia and may be an early marker for atherosclerosis in angiographically smooth arteries. The aim of the present study was to relate preoperative serum lipids to endothelium-dependent relaxation in internal mammary arteries of patients underg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00081-3
更新日期:1997-06-01 00:00:00
abstract::The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular ef...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.07.006
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:Ischemic preconditioning confers cardioprotection in early and delayed phases. We investigated the delayed window of pharmacological and ischemic preconditioning in human myocardium, and the involvement of mitoKATP, PKC and p38MAPK. METHODS:These studies were carried out using human right atrial tissue in a ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.10.013
更新日期:2004-02-15 00:00:00
abstract:AIMS:To define the molecular mechanisms of cardiotoxicity induced by Sunitinib and to identify the role of biological sex in modulating toxicity. METHODS AND RESULTS:Exposure of isolated cardiomyocytes to plasma-relevant concentrations of Sunitinib and other tyrosine kinase inhibitors produces a broad spectrum of abno...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv152
更新日期:2015-07-01 00:00:00
abstract:AIMS:Vascular inflammation is a major atherogenic factor and Toll-like receptor (TLR) 2 ligands, including bacterial and serum lipoproteins, seem to be involved in atherogenesis. On this basis, we analysed the effect of lipoproteins and different lipid components on TLR2-dependent signalling. METHODS AND RESULTS:In TL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
abstract:AIMS:The channel function of the cardiac ryanodine receptor (RyR2) is modulated by calmodulin (CaM). However, the involvement of CaM in aberrant Ca(2+) release in diseased hearts remains unclear. Here, we investigated the pathogenic role of defective CaM binding to the RyR2 in the channel dysfunction associated with he...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs271
更新日期:2012-12-01 00:00:00