Abstract:
:The genetic basis of cardiac electrical phenotypes has in the last 25 years been the subject of intense investigation. While in the first years, such efforts were dominated by the study of familial arrhythmia syndromes, in recent years, large consortia of investigators have successfully pursued genome-wide association studies (GWAS) for the identification of single-nucleotide polymorphisms that govern inter-individual variability in electrocardiographic parameters in the general population. We here provide a review of GWAS conducted on cardiac electrical phenotypes in the last 14 years and discuss the implications of these discoveries for our understanding of the genetic basis of disease susceptibility and variability in disease severity. Furthermore, we review functional follow-up studies that have been conducted on GWAS loci associated with cardiac electrical phenotypes and highlight the challenges and opportunities offered by such studies.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Glinge C,Lahrouchi N,Jabbari R,Tfelt-Hansen J,Bezzina CRdoi
10.1093/cvr/cvaa144subject
Has Abstractpub_date
2020-07-15 00:00:00pages
1620-1634issue
9eissn
0008-6363issn
1755-3245pii
5840726journal_volume
116pub_type
杂志文章abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:This study aimed to examine the effects of adenovirus-mediated expression of p35, a baculovirus gene, on apoptosis induced by hypoxia/reoxygenation (H/R) in cardiomyocytes. METHODS:Neonatal rat cardiomyocytes were infected with recombinant adenoviral vectors expressing p35 (Ad2/CMVp35) or no transgene (Ad2/C...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00412-1
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVE:A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT(1)) receptor in the carotid body (CB) are involved in the enhanced peripheral chemoreceptor sensitivity in rabbits with chronic heart failure (CHF). NADPH oxidase...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.04.006
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVE:The aim was to study the effect of thyroid hormone on collagen gene expression in the myocardium of the tight skin mouse (TSK), a genetic model of myocardial fibrosis. METHODS:Heterozygous male (TSK/+) (n = 20) and normal (+/+) homozygous mice (n = 20), 1.5-2 months old of the C57 BL/6 strain were studied. V...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.6.603
更新日期:1992-06-01 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::Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery...
journal_title:Cardiovascular research
pub_type: 社论,评审
doi:10.1016/s0008-6363(98)00244-2
更新日期:1998-12-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to record diastolic transmitral pressure gradients at high sensitivity to quantitate the effect on transmitral pressure gradients of changing the heart rate. DESIGN:Diastolic left atrial and left ventricular pressures were recorded at high sensitivity (40 mm Hg = 10 mm recorded deflection) ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.7.560
更新日期:1990-07-01 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:OBJECTIVE:The aim was to test the hypothesis that in normal humans angiotensin II would stimulate local release of noradrenaline under basal conditions or during a sympathetic stimulus provided by lower body negative pressure (LBNP). METHODS:Nine healthy volunteers received intra-arterial infusions of angiotensin II, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.5.663
更新日期:1994-05-01 00:00:00
abstract:AIMS:n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq411
更新日期:2011-05-01 00:00:00
abstract::It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac C...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.02.010
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:The mechanism of defibrillation is controversial. Reentry appearing immediately after the shock has been shown to be responsible for defibrillation failure in some studies while other studies have demonstrated that a rapid train of focal activations with the first focus appearing >50 ms after the shock is re...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.10.009
更新日期:2004-01-01 00:00:00
abstract:AIMS:Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechani...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw231
更新日期:2017-01-01 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: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:OBJECTIVE:The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS:Patie...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00261-8
更新日期:2000-01-14 00:00:00
abstract:OBJECTIVE:To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS:Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril suppl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00239-4
更新日期:1999-12-01 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:OBJECTIVE:NG,NG-dimethylarginine (asymmetric dimethylarginine, ADMA) is an important endogenous substance with potent inhibitory actions on nitric oxide (NO) synthesis. The present study was designed to determine circulating ADMA levels and endothelium-dependent, NO mediated vasodilation in a rat model of congestive he...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00242-3
更新日期:1998-03-01 00:00:00
abstract:AIMS:We investigated the molecular mechanism of rapid-depolarization-induced atrial fibrosis. METHODS AND RESULTS:We used a direct atrial myocyte-fibroblast contact co-culture and a fibroblast-specific transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) and procollagen type I α-1 (COL1A1) lu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq322
更新日期:2011-03-01 00:00:00
abstract:AIMS:Current mechanisms driving cardiac pacemaker function have focused on ion channel and gap junction channel function, which are essential for action potential generation and propagation between pacemaker cells. However, pacemaker cells also harbour desmosomes that structurally anchor pacemaker cells to each other i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw083
更新日期:2016-08-01 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::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::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: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::Studies were carried out in four different canine preparations to determine the effect of collateral flow on early changes induced by acute segmental ischaemia. The results of these experiments indicated that collateral flow provided a limited and variable amount of protection. When collateral flow was eliminated, myo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.5.309
更新日期:1978-05-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. DESIGN:Coronary arterial thrombi were induced by a copper coi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.3.184
更新日期:1991-03-01 00:00:00
abstract:OBJECTIVE:Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration. METHODS:We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting. RESULTS:As com...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.04.018
更新日期:2007-08-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common type of arrhythmia in humans, yet the genetic cause of AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants in four distinct genetic loci, and more recently, a meta-GWAS has further implicated six new loci in AF. However, the functional...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv207
更新日期:2016-01-01 00:00:00
abstract:AIMS:Apolipoprotein E (apoE) may act as a vasculoprotective factor by promoting plasma lipid clearance and cholesterol efflux. Moreover, apoE accumulates at sites of vascular injury and modulates the effect of growth factors on smooth muscle cells (SMCs). Experimental data suggested that hypothalamic apoE expression is...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt126
更新日期:2013-08-01 00:00:00