Abstract:
:In this review, we summarize current knowledge on the genetics of coronary artery disease, based on 10 years of genome-wide association studies. The discoveries began with individual studies using 200K single nucleotide polymorphism arrays and progressed to large-scale collaborative efforts, involving more than a 100 000 people and up to 40 Mio genetic variants. We discuss the challenges ahead, including those involved in identifying causal genes and deciphering the links between risk variants and disease pathology. We also describe novel insights into disease biology based on the findings of genome-wide association studies. Moreover, we discuss the potential for discovery of novel treatment targets through the integration of different layers of 'omics' data and the application of systems genetics approaches. Finally, we provide a brief outlook on the potential for precision medicine to be enhanced by genome-wide association study findings in the cardiovascular field.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Erdmann J,Kessler T,Munoz Venegas L,Schunkert Hdoi
10.1093/cvr/cvy084subject
Has Abstractpub_date
2018-07-15 00:00:00pages
1241-1257issue
9eissn
0008-6363issn
1755-3245pii
4956758journal_volume
114pub_type
历史文章,杂志文章,评审abstract:STUDY OBJECTIVE:The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.10.875
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVE:The K(+) channel encoded by the human ether-a-go-go-related gene (HERG) is crucial for repolarization in the human heart. In order to investigate the impact of HERG current (I(Kr)) on the incidence of cardiac arrhythmias, we generated a transgenic mouse expressing HERG specifically in the heart. METHODS AND ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.09.030
更新日期:2005-01-01 00:00:00
abstract::Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. It is becoming increasingly clear that microRNAs (miRNAs or miRs), a group of highly conserved small (∼18-24 nucleotide) no...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr291
更新日期:2012-05-01 00:00:00
abstract::The potent anaphylatoxin C3a was measured in the peripheral blood of eleven patients receiving radiocontrast agents whilst undergoing coronary angiography. In seven patients C3a levels were raised during this procedure and in three of these the anaphylatoxin was increased between four and tenfold. In four patients C3a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.85
更新日期:1985-02-01 00:00:00
abstract::Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed 'ischaemia and no obstructive ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvaa002
更新日期:2020-03-01 00:00:00
abstract:AIMS:Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (LmnaH222P/H222P). The ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt106
更新日期:2013-08-01 00:00:00
abstract:AIM:Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm069
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 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::CaMKII is a serine-threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflamm...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw002
更新日期:2016-04-01 00:00:00
abstract:AIM:To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS:ET-1 (0.013 microg/min) was infused to male ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00657-0
更新日期:2003-01-01 00:00:00
abstract::The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.7.536
更新日期:1986-07-01 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:We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients. METHODS AND RESULTS:ApoE(-/-)RAG2(-/-) mice received four intravenous injections of sa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm034
更新日期:2008-02-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate whether basal coronary vascular tone and myocardial perfusion depend upon endothelial nitric oxide (NO) synthesis. DESIGN:Myocardial blood flow and vascular resistance of the left and right ventricles were studied before and after intravenous infusions of either NG-nitro-L-ar...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.8.700
更新日期:1991-08-01 00:00:00
abstract:AIMS:Chronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca(2+) channels (LCCs) in the plasma membrane (including transverse tubules, TTs) and the ryanodine receptors (RyRs) in the sarcoplasmic reticul...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt030
更新日期:2013-05-01 00:00:00
abstract:AIMS:The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic disease...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw172
更新日期:2016-10-01 00:00:00
abstract::Ischemia-reperfusion of the heart and other organs results in the accumulation of unesterified arachidonic acid (AA) via the action of membrane-bound phospholipases, primarily phospholipase A2. AA can be metabolized by the classical cyclooxygenase (COX) and lipoxygenase (LOX) pathways to well-characterized metabolites...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.06.007
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVES:Early thrombolysis can reduce infarct size and enhance the long term recovery of contractile function after acute myocardial infarction. These benefits of early reperfusion may be confounded, however, by platelet mediated reocclusion after initial lysis, and "reperfusion injury" mediated by oxygen derived fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.925
更新日期:1993-06-01 00:00:00
abstract::We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular ca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1758
更新日期:1993-10-01 00:00:00
abstract:CONDENSED ABSTRACT:We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00164-3
更新日期:1998-12-01 00:00:00
abstract:AIMS:Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr158
更新日期:2011-10-01 00:00:00
abstract::Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy006
更新日期:2018-03-15 00:00:00
abstract::We have used a miniature cadmium telluride detector in the assessment of muscle blood flow during dynamic exercise in man following local injection of 133Xenon. The results obtained were compared with those using a conventional sodium iodide detector. There was no significant difference between the results obtained wi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.12.731
更新日期:1981-12-01 00:00:00
abstract::An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.95
更新日期:1985-02-01 00:00:00
abstract::The effects of repeated (10 X), brief Ca2+-free perfusions (20 to 120 s) on myocardial contractility, coronary flow and release of cellular constituents of isolated rat heart were investigated. Ten successive Ca2+-deprivations of 20 or 40 s had no irreversible influences on cardiac performance. Ca2+-deprivations, howe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.8.476
更新日期:1983-08-01 00:00:00
abstract:AIMS:Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key compone...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt265
更新日期:2014-03-01 00:00:00
abstract:AIMS:Antihypertensive drugs are included in the medical therapy of vascular Ehlers-Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist lo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz095
更新日期:2020-02-01 00:00:00
abstract::The effect of circulation time on plasma high density lipoprotein cholesterol concentrations was investigated in 20 male Wistar rats injected with alcohol, stressed with lighting, or fed a high fat diet. Circulation time was measured during anaesthesia with a computerised dichromatic earpiece densitometer. Indocyanine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.5.368
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVE:Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily and are key regulators of fatty acid oxidation (FAO) in the heart. Systemic carnitine deficiency (SCD) causes disorders of FAO and induces hypertrophic cardiomy...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.02.005
更新日期:2006-06-01 00:00:00