Abstract:
OBJECTIVE:Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness in addition to cardiac arrhythmias. In this study, we investigate and discuss dominant-negative I(Ks) current reduction by a KCNQ1 deletion mutation identified in a RWS family. METHODS:Single-strand conformation polymorphism analysis and direct sequencing were used to screen LQTS genes for mutations. Mutant KCNQ1 channels were heterologously expressed in Xenopus oocytes, and potassium currents were recorded using the two-microelectrode voltage clamp technique. RESULTS:A heterozygous deletion of three nucleotides (CTT) identified in the KCNQ1 gene caused the loss of a single phenylalanine residue at position 339 (KCNQ1-deltaF339). Electrophysiological measurements in the presence and absence of the regulatory beta-subunit KCNE1 revealed that mutant and wild type forms of an N-terminal truncated KCNQ1 subunit (isoform 2) caused much stronger dominant-negative current reduction than the mutant form of the full-length KCNQ1 subunit (isoform 1). CONCLUSION:This study highlights the functional relevance of the truncated KCNQ1 splice variant (isoform 2) in establishment and mode of inheritance in long QT syndrome. In the RWS family presented here, the autosomal-dominant trait is caused by multiple dominant-negative effects provoked by heteromultimeric channels formed by wild type and mutant KCNQ1-isoforms in combination with KCNE1.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Thomas D,Wimmer AB,Karle CA,Licka M,Alter M,Khalil M,Ulmer HE,Kathöfer S,Kiehn J,Katus HA,Schoels W,Koenen M,Zehelein Jdoi
10.1016/j.cardiores.2005.05.003subject
Has Abstractpub_date
2005-08-15 00:00:00pages
487-97issue
3eissn
0008-6363issn
1755-3245pii
S0008-6363(05)00229-4journal_volume
67pub_type
杂志文章abstract:BACKGROUND:Alkalinizing agents reverse cardiotoxicity of a variety of sodium channel blockers, including tricyclic antidepressants, but their mechanisms of action are poorly understood. PURPOSE:To establish the mechanisms by which alkalinization diminishes the sodium channel blocking action of imipramine. METHODS:The...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00011-x
更新日期:1998-05-01 00:00:00
abstract:OBJECTIVE:The aim was to study (1) the effects of intracoronary saralasin, an angiotensin II receptor antagonist, on ischaemia induced and reperfusion induced regional cardiac noradrenaline release and ventricular arrhythmias; and (2) the implication of angiotensin II in coronary constriction during myocardial ischaemi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.10.968
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVES:Gap junctions have been demonstrated ultrastructurally in cardiac regions where connexin40 (Cx40) and connexin43 (Cx43) protein could not be detected immunohistochemically. We investigated therefore the distribution of their mRNAs with more sensitive techniques. METHODS:In situ hybridizations with Cx40 and ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00131-9
更新日期:1996-11-01 00:00:00
abstract::Oxygen-derived free radicals are thought to contribute to the initiation and progression of cardiovascular disease via several different mechanisms, such as consumption of nitric oxide, oxidation of proteins and lipids, and activation of redox-sensitive signalling cascades. Vascular NADPH oxidases are important source...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.08.007
更新日期:2005-01-01 00:00:00
abstract:AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp043
更新日期:2009-04-01 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:AIMS:The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in pati...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz345
更新日期:2021-01-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN:Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetis...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.5.353
更新日期:1991-05-01 00:00:00
abstract::Congenital coronary artery anomalies are of major significance in clinical cardiology and cardiac surgery due to their association with myocardial ischaemia and sudden death. Such anomalies are detectable by imaging modalities and, according to various definitions, their prevalence ranges from 0.21 to 5.79%. This cons...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv251
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:Co-expression of the KvLQT1 and minK potassium channel subunits is required to recapitulate I(Ks), the slow component of the cardiac delayed rectifier current, and mutations in either gene cause the congenital Long QT syndrome. It is becoming increasingly well-recognized that multiprotein channel complexes co...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00498-4
更新日期:2002-10-01 00:00:00
abstract::Hyponatremia is a frequent electrolyte disorder. It is often found in congestive cardiac failure, liver cirrhosis, plasma volume contraction and in SiADH. In these disorders hyponatremia is caused by nonosmotic vasopressin and sustained fluid intake. This provides a rationale for V2 vasopressin receptor antagonists in...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00288-7
更新日期:2001-08-15 00:00:00
abstract::The cardiac SR Ca(2+)-ATPase (SERCA2a) regulates intracellular Ca(2+)-handling and thus, plays a crucial role in initiating cardiac contraction and relaxation. SERCA2a may be modulated through its accessory phosphoprotein phospholamban or by direct phosphorylation through Ca(2+)/calmodulin dependent protein kinase II ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(02)00694-6
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:Gap junction channels provide for direct electrical coupling between cells, and play an important role in homeostasis and electrical coupling. One of the proteins that form gap junctions, Connexin40 (Cx40), shows restricted expression in the body, and is found in blood vessels and in the atrium and conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00373-9
更新日期:2000-03-01 00:00:00
abstract:AIMS:A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa205
更新日期:2020-07-16 00:00:00
abstract::The heart contains not only cardiomyocytes but also other cell types such as endothelial cells and fibroblasts. Functional crosstalk among these cell types is important for normal cardiac function and is also involved in disease pathophysiology. Recent data indicate that redox signalling within and between endothelial...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu050
更新日期:2014-05-01 00:00:00
abstract:AIMS:Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz306
更新日期:2020-10-01 00:00:00
abstract::Gender has an important influence on blood pressure, with premenopausal women having a lower arterial blood pressure than age-matched men. Compared with premenopausal women, postmenopausal women have higher blood pressures, suggesting that ovarian hormones may modulate blood pressure. However, whether sex hormones are...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00527-2
更新日期:2002-02-15 00:00:00
abstract:AIMS:Animal studies show that transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). This study investigated the role of TGF-β1 in human AF and the mechanism of atrial-selective fibrosis. METHODS AND RESULTS:Atrial specimens from 17 open heart surgery patients ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt074
更新日期:2013-09-01 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:AIMS:Doxorubicin (DOX) is widely used in cytostatic treatments, although it may cause cardiovascular dysfunction as a side effect. DOX treatment leads to enhanced free radical production that in turn causes DNA strand breakage culminating in poly(ADP-ribose) polymerase (PARP) activation and mitochondrial and cellular d...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr246
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVES:We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). METHODS:We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.03.017
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND:The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00345-9
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVE:The aim was to establish whether the duration of coronary ischaemia and coronary ischaemia with reperfusion selectively reduced the magnitude of relaxation mediated by endothelium dependent relaxing factor (EDRF) in response to thrombin, compared with relaxation produced by acetylcholine and calcimycin. METH...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.3.250
更新日期:1992-03-01 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::Arteriogenesis, the process of collateral artery growth as an adaptation to major arterial occlusion, can be life- and tissue saving and may alter the natural course of the consequences and organ manifestations of arterial disease. This is achieved by an active growth process that is coupled to complete arterial remod...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00191-1
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:It has been suggested that nitric oxide (NO) is involved in the regulation of myocardial function in a variety of diseases such as dilated cardiomyopathy, myocarditis, heart transplant rejection, and septic shock. However, the underlying mechanism of NO mediated reduction of cardiac contractility has not been...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00149-1
更新日期:1997-11-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to determine whether the deleterious effects of anaesthesia on cardiac muscle function were due to disturbance of protein synthesis. Comparative investigations were made on anaerobic and aerobic skeletal muscles, and plasma insulin and growth hormone levels were also measured to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.4.314
更新日期:1991-04-01 00:00:00
abstract:AIMS:Despite the observation that ErbB2 regulates sensitivity of the heart to doxorubicin or ErbB2-targeted cancer therapies, mechanisms that regulate ErbB2 expression and activity have not been studied. Since isoproterenol up-regulates ErbB2 in kidney and salivary glands and β2AR and ErbB2 complex in brain and heart, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv274
更新日期:2016-03-01 00:00:00
abstract::Controversy exists as to whether the diabetic heart is more or less sensitive to ischemic injury. Although a considerable number of experimental studies have directly determined the effects of ischemia on the diabetic heart, there is still no general agreement as to whether metabolic changes within the myocardium cont...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00037-0
更新日期:1997-04-01 00:00:00
abstract:AIMS:Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that cont...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt057
更新日期:2013-07-01 00:00:00