Abstract:
:Cardiovascular diseases are among the main causes of morbidity and mortality in Western countries and considered as a leading public health issue. Therefore, there is a strong need for new disease models to support the development of novel therapeutics approaches. The successive improvement of genome editing tools with zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and more recently with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) has enabled the generation of genetically modified cells and organisms with much greater efficiency and precision than before. The simplicity of CRISPR/Cas9 technology made it especially suited for different studies, both in vitro and in vivo, and has been used in multiple studies evaluating gene functions, disease modelling, transcriptional regulation, and testing of novel therapeutic approaches. Notably, with the parallel development of human induced pluripotent stem cells (hiPSCs), the generation of knock-out and knock-in human cell lines significantly increased our understanding of mutation impacts and physiopathological mechanisms within the cardiovascular domain. Here, we review the recent development of CRISPR-Cas9 genome editing, the alternative tools, the available strategies to conduct genome editing in cardiovascular cells with a focus on its use for correcting mutations in vitro and in vivo both in germ and somatic cells. We will also highlight that, despite its potential, CRISPR/Cas9 technology comes with important technical and ethical limitations. The development of CRISPR/Cas9 genome editing for cardiovascular diseases indeed requires to develop a specific strategy in order to optimize the design of the genome editing tools, the manipulation of DNA repair mechanisms, the packaging and delivery of the tools to the studied organism, and the assessment of their efficiency and safety.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Vermersch E,Jouve C,Hulot JSdoi
10.1093/cvr/cvz250subject
Has Abstractpub_date
2020-04-01 00:00:00pages
894-907issue
5eissn
0008-6363issn
1755-3245pii
5581353journal_volume
116pub_type
杂志文章,评审abstract:OBJECTIVE:Acute ischemia comes with two phases of life-threatening arrhythmias, early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The mechanism of the latter is unknown and in this paper, we test the hypothesis that a phase of intermediate coupling between surviving epicardium and inexcitable midmyoc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00222-x
更新日期:2001-05-01 00:00:00
abstract:OBJECTIVE:The mechanism of spontaneous myogenic tone was investigated in isolated arteriolar segments. METHODS:Arterioles were isolated from rat cremaster muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constricted from a passive dia...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00161-8
更新日期:1999-01-01 00:00:00
abstract:OBJECTIVE:The aim of the presented method was the characterization of different complex heart rate dynamics in conscious rabbits as well as during general anaesthesia and vagal blockade. This was done by non-linear prediction of original measured and special surrogate data in the phase space. METHOD:The development of...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Reperfusion of the heart after a period of ischaemia leads to the opening of a nonspecific pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore (MPTP). This transition causes mitochondria to become uncoupled and capable of hydrolysing rather than synthesising ATP. Unrestrai...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/S0008-6363(03)00533-9
更新日期:2004-02-15 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
abstract:OBJECTIVES:Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history". This previous-beat contraction history, which appears to be an interplay between the mechanical events of o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::The effect of lidocaine on the effective refractory period of the right ventricle (EVRP) was measured in 10 patients using the extra stimulus technique of progressive introduction of premature stimuli until a response could not be elicited. In four patients lidocaine produced a significant decrease in the EVRP, in a f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.5.621
更新日期:1975-09-01 00:00:00
abstract::Because of ventricular interdependence, part of the measured left ventricular diastolic pressure can be attributed to the right ventricle. Therefore, we examined the hypothesis that left ventricular diastolic properties are modified by alterations in right ventricular compliance and pressure even without a change in r...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.11.768
更新日期:1988-11-01 00:00:00
abstract::Cardiac hypertrophy occurs in a number of disease states associated with chronic increases in cardiac work load. Although cardiac hypertrophy may initially represent an adaptive response of the myocardium, ultimately, it often progresses to ventricular dilatation and heart failure. Much investigation has focused on th...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.04.002
更新日期:2004-08-15 00:00:00
abstract:AIMS:Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is caused by mutations in the cardiac ryanodine receptor (RyR2) that lead to disrupted Ca(2+) handling in cardiomyocytes and ventricular tachycardia. The aim of this study was to test whether exercise training could reduce the propensity for arrh...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw095
更新日期:2016-08-01 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::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:AIMS:Treatment with the anticancer drug taxol (TXL), which polymerizes the cytoskeleton protein tubulin, may evoke cardiac arrhythmias based on reduced human cardiac sodium channel (Na(v)1.5) function. Therefore, we investigated whether enhanced tubulin polymerization by TXL affects Na(v)1.5 function and expression and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp352
更新日期:2010-03-01 00:00:00
abstract:AIMS:A cytosolic calcium (Ca(2+)(i)) increase is an important activation signal for the endothelium. We investigated whether interendothelial spreading of the Ca(2+) signal via gap junctions (GJs) plays a role for the overall Ca(2+)(i) increase in response to vasoactive agonists. METHODS AND RESULTS:In human umbilical...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr345
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasingly apparent is tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn054
更新日期:2008-07-15 00:00:00
abstract:OBJECTIVE:Smooth muscle cell proliferation and migration are the predominant responses to intimal and medial injury after percutaneous transluminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that the antiproliferative effect of heparin in...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.7.1209
更新日期:1993-07-01 00:00:00
abstract:AIMS:The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined. METHODS AND RESULTS:Whole-cell patch-clamp recordings showed outward-rectifying currents in hum...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp153
更新日期:2009-08-01 00:00:00
abstract:AIMS:in this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. METHODS AND RESULTS:we created a myocardial ischaemia-reperfusion model in 60 C57/BL ma...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq269
更新日期:2011-01-01 00:00:00
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:The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS:Experiments were done on fragments of papillary muscles from the right ventricles of gu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.371
更新日期:1992-04-01 00:00:00
abstract::Sprouting angiogenesis is an invasive process that involves proteolytic activities required for the degradation of the endothelial basement membrane, cell migration with removal of obstructing matrix proteins, and generation of space in the matrix to allow endothelial cells to form a proper lumen. In the last decade i...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm102
更新日期:2008-05-01 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::To test hypothesis that adrenergic neurotransmission is impaired in acute myocardial ischaemia, we studied contractile function of normal and ischaemic myocardium after coronary artery occlusion. For each area we compared the contractile response to left sympathetic nerve stimulation (LSS) with the response to exogeno...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.2.116
更新日期:1980-02-01 00:00:00
abstract:AIMS:Moderate wine consumption is associated with a significant reduction of cardiovascular mortality. The molecular basis of this phenomenon remains unknown. Platelet-derived growth factor (PDGF) is an important contributor to atherogenesis. We investigated the effects of selected red and white wines on PDGF receptor ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn340
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:Temporal effects of prolonged hypoxaemia and reoxygenation, on the systemic pulmonary and mesenteric circulations in newborn piglets, were investigated. METHODS:Two groups [control (n = 5), hypoxaemic (n = 7)] of 1-3 day old anaesthetised piglets were instrumented with ultrasound flow probes placed to measur...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00080-7
更新日期:1998-08-01 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::A growing body of animal studies provides evidence for potential cardioprotective effects of inhibitors of the enzyme phosphodiesterase isoform 5. Infarct size reduction by administration of phosphodiesterase 5 inhibitors was described in various experimental models of ischaemia and reperfusion. Furthermore, potential...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp170
更新日期:2009-07-15 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:AIMS:Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs186
更新日期:2012-08-01 00:00:00