Abstract:
OBJECTIVE:Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited long QT syndrome (LQTS) characterised by profound sensorineural deafness and predisposition to syncope and sudden cardiac death. Mutation analysis has established the presence of mutations in affected individuals in the genes KCNQ1 and KCNE1: the potassium channel complex responsible for the cardiac I(Ks) current involved in repolarisation of the ventricular action potential. Our objective was to determine the functional effects of disease causing mutations in JLNS. METHODS:In this study we have investigated the electrophysiological effects of eight distinct JLNS mutations after expression of cRNA in Xenopus laevis oocytes. RESULTS:KCNE1 mutant T59P/L60P showed no dominant negative effect and was a pure loss of function mutation. KCNQ1 mutant E261D showed a strong dominant-negative effect. KCNQ1 mutant R243H produced a moderate dominant-negative effect, right shifted the steady-state activation curve and led to an increased deactivation rate. The behaviour of KCNQ1 mutants 572-576del, 1008delC, R518X, Q530X, R594Q depended on the relative quantities of mutant and wild-type proteins (with a weak dominant-negative effect present at 1:3 but not 1:1 injection ratios). These data indicate the presence of an additional assembly domain before S2-S3 and the importance of the S4-S5 region in channel function and gating. CONCLUSIONS:Our data suggest a spectrum of behaviour for disease causing mutations from simple loss of function through to prominent dominant negative behaviour.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Huang L,Bitner-Glindzicz M,Tranebjaerg L,Tinker Adoi
10.1016/s0008-6363(01)00350-9subject
Has Abstractpub_date
2001-09-01 00:00:00pages
670-80issue
4eissn
0008-6363issn
1755-3245pii
S0008636301003509journal_volume
51pub_type
杂志文章abstract::The central role of vascular endothelial growth factor (VEGF) in angiogenesis in health and disease makes it attractive both as a therapeutic target for anti-angiogenic drugs and as a pro-angiogenic cytokine for the treatment of ischaemic heart disease. While VEGF binds to two receptor protein tyrosine kinases, VEGFR1...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00268-6
更新日期:2001-02-16 00:00:00
abstract:OBJECTIVE:Preexposure of macrophages to oxidized low-density lipoprotein (oxLDL) attenuates formation of reactive oxygen species (ROS) upon stimulation with phorbol 12-myristate 13-acetate (PMA) or acute exposure to oxLDL. We examined whether attenuation of the oxidative burst is attributed to down-regulation of protei...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.05.023
更新日期:2006-08-01 00:00:00
abstract:UNLABELLED:Recent investigations have established the feasibility of using exogenously delivered angiogenic growth factors to increase collateral artery development in animal models of myocardial and hindlimb ischemia. OBJECTIVE:Our aim was to evaluate the ability of a stabilized form of acidic fibroblast growth facto...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00522-4
更新日期:2003-10-01 00:00:00
abstract::The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.10.649
更新日期:1985-10-01 00:00:00
abstract::In the superior vena cava of anaesthetised open chest dogs the axial pressure gradient was measured simultaneously with the blood flow velocity under different preload conditions. Both pressure gradient and velocity curves showed distinct systolic and diastolic waves. Peak pressure gradient ranged between 26 and 93 Pa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.12.935
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVE:To explore long-term cardiac phenotype in transgenic (TG) mice with 300-fold overexpression of beta(2)-adrenergic receptors (AR). METHODS:Echocardiography was performed serially on a cohort of wild-type and TG mice (n=26 each) between 4 and 15 months of age. Survival was monitored and autopsy and histologica...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00187-5
更新日期:2000-12-01 00:00:00
abstract:AIMS:Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca(2+). We investigated whether this represents partial or complete reversal of cellular remodelling. METHODS AND RESULTS:Mice with MI following left coronary ligation were given free access...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp381
更新日期:2010-04-01 00:00:00
abstract::The effect of catheterisation on the rabbit aortic wall is investigated employing a technique identical to that used for continuous monitoring of blood pressure in humans. The catheters were introduced into the aorta through the right femoral artery of the rabbit using the Seldinger technique, except that the catheter...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.9.541
更新日期:1979-09-01 00:00:00
abstract::In acute myocardial infarction (MI), reactive oxygen species (ROS) are generated in the ischaemic myocardium especially after reperfusion. ROS directly injure the cell membrane and cause cell death. However, ROS also stimulate signal transduction to elaborate inflammatory cytokines, e.g. tumour necrosis factor-alpha (...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn335
更新日期:2009-02-15 00:00:00
abstract::There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Bloo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.12.734
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVE:Norepinephrine (NE) induced hypertrophy and remodelling of the extracellular matrix (ECM) in the left ventricle (LV) of the rat heart with resulting fibrosis. However, there was no increased collagen deposition in the right ventricle (RV). To test the hypothesis that lack of RV fibrosis is the result of eleva...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00700-9
更新日期:2003-02-01 00:00:00
abstract::18 patients without valvular pathology, coronary artery disease, or idiopathic hypertrophic subaortic stenosis were haemodynamically and angiographically investigated in order to analyse the effects of a ventricular extrasystolic beat upon the post-extrasystolic left ventricular peak pressure. In eight normal patients...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.6.338
更新日期:1979-06-01 00:00:00
abstract:OBJECTIVE:Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS:Right atrial appendages were obtained from eight patients with paroxysmal AF, ten ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00045-0
更新日期:1999-05-01 00:00:00
abstract:AIMS:Our objective was to explore the functional interdependence of protein kinase A (PKA) phosphorylation with binding of modulatory FK506 binding proteins (FKBP12/12.6) to the ryanodine receptor (RyR). RyR type 1 or type 2 was prepared from rabbit skeletal muscle or pig cardiac muscle, respectively. In heart failure,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp273
更新日期:2010-01-01 00:00:00
abstract::Increased Na/Ca exchange (NCX) expression may be part of the genetic reprogramming in cardiac remodeling. In this review we address the following questions: (1) Is increased NCX activity a general feature of cardiac remodeling in hypertrophy and heart failure? (2) How does this contribute to the contractile and electr...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00470-9
更新日期:2002-03-01 00:00:00
abstract::The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptor...
journal_title:Cardiovascular research
pub_type: 评论,杂志文章,评审
doi:10.1016/s0008-6363(99)00319-3
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Insulin protects cardiomyocytes from apoptosis. Insulin resistance usually refers to a defect in the ability of insulin to stimulate glucose uptake. It is unknown, however, whether or not insulin resistance compromises the cell-protective effect of the hormone. Caspases are a family of cysteine proteases that...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.012
更新日期:2007-12-01 00:00:00
abstract:AIMS:This study aimed at characterizing expression and the functional role of the Gjb6 gene, encoding for connexin 30 (Cx30) protein, in the adult mouse heart. METHODS AND RESULTS:The expression of the Gjb6 gene in the mouse heart was investigated by RT-PCR and sequencing of amplified cDNA fragments. The sites of Gjb6...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp280
更新日期:2010-01-01 00:00:00
abstract::Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Di...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.2.232
更新日期:1976-03-01 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:STUDY OBJECTIVE:The aim was to determine whether taurine influences the membrane surface charges in cardiac muscle. DESIGN:Screening of the negative charges at the outside surface of the membrane results in a shift of the steady state inactivation of the sodium system towards less negative potentials. This feature was...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.11.918
更新日期:1990-11-01 00:00:00
abstract:OBJECTIVE:In heart failure (HF), the generation of reactive oxygen species (ROS) is enhanced. It was shown that failing cardiac myocytes are more susceptible to ROS-induced damage, possibly due to increased expression of the sarcolemmal Na-Ca exchanger (NCX). METHODS:We investigated the consequences of increased expre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.08.006
更新日期:2003-11-01 00:00:00
abstract:AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr145
更新日期:2011-10-01 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:OBJECTIVES:To characterize the 'anti-ischemic' effects of adenosine metabolism inhibition in ischemic-reperfused myocardium. METHODS:Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 microM erythro-2-(2-hydroxy-3-nonyl)ad...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00360-1
更新日期:2001-10-01 00:00:00
abstract::The effects of increasing oxygen tension from fetal to neonatal levels and of incubation in the cyclo-oxygenase inhibitor, indomethacin, on the response of isolated rings of neonatal rabbit ductus arteriosus and aorta to noradrenaline were studied in vitro. Increasing oxygen tension did not affect the sensitivity, as ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.12.910
更新日期:1988-12-01 00:00:00
abstract::To evaluate the effect of beta blockade on energy metabolism in ischaemic myocardium metoprolol tartrate in doses of 0.2 or 0.5 mg.kg-1 or saline was injected into 24 anaesthetised dogs 20 min after coronary ligation. Regional myocardial blood flow was measured by the hydrogen gas clearance method, and the heart rate ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.9.660
更新日期:1987-09-01 00:00:00
abstract:OBJECTIVE:R 75,231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.1.111
更新日期:1993-01-01 00:00:00
abstract::Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.1.45
更新日期:1979-01-01 00:00:00
abstract::An oscillatory current (Ios) can be recorded after depolarising clamps of a given amplitude and duration. To determine whether Ios depends on other currents activated during the clamp, the Ios was investigated in the absence and in the presence of 4-aminopyridine (4-AP) and cesium (Cs). The following results were obta...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.11.637
更新日期:1982-11-01 00:00:00