Abstract:
:Stroke, ischaemic stroke and subtypes of ischaemic stroke display substantial heritability. When compared with related vascular conditions, the number of established risk loci reaching genome-wide significance for association with stroke is still in the lower range, particularly for aetiological stroke subtypes such as large artery atherosclerotic stroke or small vessel stroke. Nevertheless, for individual loci substantial progress has been made in determining the specific mechanisms mediating stroke risk. In this review, we present a roadmap for functional follow-up of common risk variants associated with stroke. First, we discuss in silico strategies for characterizing signals in non-coding regions and highlight databases providing information on quantitative trait loci for mRNA and protein expression, as well as methylation, focussing on those with presumed relevance for stroke. Next, we discuss experimental strategies for following up on non-coding risk variants and regions such as massively parallel reporter assays, proteome-wide association studies, and chromatin conformation capture (3C) assays. These and other approaches are relevant for gaining insight into the specific variants and mechanisms mediating genetic stroke risk. Finally, we discuss how genetic findings could influence clinical practice by adding to diagnostic algorithms and eventually improve treatment options for stroke.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Malik R,Dichgans Mdoi
10.1093/cvr/cvy068subject
Has Abstractpub_date
2018-07-15 00:00:00pages
1226-1240issue
9eissn
0008-6363issn
1755-3245pii
4938588journal_volume
114pub_type
杂志文章,评审abstract::The signal transducer and activator of transcription 3 (STAT3) is fundamental for physiological homeostasis and stress-induced remodelling of the heart as deregulated STAT3 circuits are sufficient to induce dilated and peripartum cardiomyopathy and adverse remodelling after myocardial infarction. STAT3 activity depend...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu034
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:Sphingosine 1-phosphate is a naturally occurring biologically active lysophospholipid. Recent studies suggested that sphingosine 1-phosphate is released into the blood flow from activated platelets upon stimulation to exert multiple biological phenomenon. The purpose of this study was to assess the effects of...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00013-4
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVE:Inducible costimulator (ICOS) is a member of the CD28 family. Although inflammation is an essential pathological feature of myocarditis, the role of ICOS in myocarditis remains unclear. METHODS AND RESULTS:Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00334-1
更新日期:2003-07-01 00:00:00
abstract::Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-tr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw037
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+(ATP)) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+(ATP) channels. METHODS:Guinea pig ventricular myocytes were isolated using collagenase digestion....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00092-8
更新日期:1997-08-01 00:00:00
abstract:OBJECTIVE:This study was conducted to evaluate to what extent the ischemia-reperfusion injury resulting from the cardiopulmonary bypass (CPB) and aortic cross-clamping procedures during coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response generally found in these patients. METHODS:S...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00403-4
更新日期:2000-03-01 00:00:00
abstract::This study has investigated the origin of the pulsatile expansion of the forearm recorded by the amplification of the pulsatile signal derived from a mercury in rubber plethysmograph. Venous occlusion to pressures of 40 mmHg had no effect on the amplitude of the volume pulse, suggesting that the volume pulse originate...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.11.651
更新日期:1984-11-01 00:00:00
abstract::STUDY OBJECTIVE - The objective was to measure platelet function in vivo (as cutaneous bleeding time), the role of catecholamines, and the effect of inhibiting thromboxane synthesis on bleeding time, in patients with myocardial infarction, unstable angina, and non-cardiac chest pain. DESIGN - Haemotological variables ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.1.19
更新日期:1990-01-01 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::One of the striking differences that distinguish the adult from the embryonic heart in mammals and set it apart from the heart in urodeles and teleosts is the incapacity of cardiomyocytes to respond to damage by proliferation. While the molecular reasons underlying these characteristics still await elucidation, mounti...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu057
更新日期:2014-05-01 00:00:00
abstract:AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce T...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr102
更新日期:2011-08-01 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: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: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:AIMS:To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS:Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa241
更新日期:2020-08-10 00:00:00
abstract::An analytical formulation has been developed which allows the computation of mitral valve area (A) from the potentially noninvasive paramaeters of hear rate (R), cardiac output (CO) and diastolic filling period (DFP) by the equation A = 21 CO/R x DFP2. The computed areas correlate with autopsy and open heart measureme...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.4.223
更新日期:1980-04-01 00:00:00
abstract:OBJECTIVE:To investigate the cellular mechanisms underlying global and regional LV dysfunction in the post-infarct (MI) remodeled rat hearts. METHODS:LV remodeling and function were quantified by echocardiography, morphometry, in vivo hemodynamics, and isolated perfused heart studies in 6 weeks post-MI and sham-operat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00160-7
更新日期:2000-10-01 00:00:00
abstract:OBJECTIVE:Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.006
更新日期:2005-09-01 00:00:00
abstract::Cardiomyocyte death secondary to transient ischaemia occurs mainly during the first minutes of reperfusion in the form of contraction band necrosis. Research on the mechanisms leading to sarcolemmal rupture and necrosis during initial reperfusion identified several promising pharmacological targets directed either to ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp109
更新日期:2009-07-15 00:00:00
abstract:AIMS:Cardiovascular research requires complex and functionally intact experimental models. Due to major differences in the cellular and subcellular composition of the myocardium between species, the use of human heart tissue is highly desirable. To enhance the experimental use of the human myocardium, we established me...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr259
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the possible role of prostacyclin (PGI2) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). METHODS:Measurement of mRNA and protein levels of PGH synthase (PGHS)-1, PGI2 synthase and the PGI2 receptor, in the thoracic aorta was performed in SHR...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00239-9
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis. METHO...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.06.015
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVES:Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.11.001
更新日期:2007-02-01 00:00:00
abstract::The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol.kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate so...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.8.537
更新日期:1988-08-01 00:00:00
abstract:OBJECTIVES:While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed form...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract:Aims:Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy167
更新日期:2018-11-01 00:00:00
abstract::The most critical determinant of prognosis in patients with acute myocardial infarction (MI) is infarct magnitude, which can be established within several hours of an attack. The importance of the subsequent healing process is not negligible, however. In fact, much experimental and clinical evidence suggests that late...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp032
更新日期:2009-07-15 00:00:00
abstract:OBJECTIVE:We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS:Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the follo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00455-8
更新日期:2002-08-15 00:00:00
abstract:OBJECTIVE:The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects. METHODS:Transmembrane action potentials and electrograms were recorded fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.11.1662
更新日期:1994-11-01 00:00:00
abstract::Vascular endothelial growth factors (VEGFs) are key regulators of permeability. The principal evidence behind how they increase vascular permeability in vivo and in vitro and the consequences of that increase are addressed here. Detailed analysis of the published literature has shown that in vivo and in vitro VEGF-med...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq105
更新日期:2010-07-15 00:00:00