Abstract:
AIMS:Regulated cell death is a main contributor of myocardial ischaemia-reperfusion (IR) injury during acute myocardial infarction. In this context, targeting apoptosis could be a potent therapeutical strategy. In a previous study, we showed that DAXX (death-associated protein) was essential for transducing the FAS-dependent apoptotic signal during IR injury. The present study aims at evaluating the cardioprotective effects of a synthetic peptide inhibiting FAS:DAXX interaction. METHODS AND RESULTS:An interfering peptide was engineered and then coupled to the Tat cell penetrating peptide (Tat-DAXXp). Its internalization and anti-apoptotic properties were demonstrated in primary cardiomyocytes. Importantly, an intravenous bolus injection of Tat-DAXXp (1 mg/kg) 5 min before reperfusion in a murine myocardial IR model decreased infarct size by 48% after 24 h of reperfusion. In addition, Tat-DAXXp was still efficient after a 30-min delayed administration, and was completely degraded and eliminated within 24 h thereby reducing risks of potential side effects. Importantly, Tat-DAXXp reduced mouse early post-infarction mortality by 67%. Mechanistically, cardioprotection was supported by both anti-apoptotic and pro-survival effects, and an improvement of myocardial functional recovery as evidenced in ex vivo experiments. CONCLUSIONS:Our study demonstrates that a single dose of Tat-DAXXp injected intravenously at the onset of reperfusion leads to a strong cardioprotection in vivo by inhibiting IR injury validating Tat-DAXXp as a promising candidate for therapeutic application.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Boisguérin P,Covinhes A,Gallot L,Barrère C,Vincent A,Busson M,Piot C,Nargeot J,Lebleu B,Barrère-Lemaire Sdoi
10.1093/cvr/cvz145subject
Has Abstractpub_date
2020-03-01 00:00:00pages
633-644issue
3eissn
0008-6363issn
1755-3245pii
5506627journal_volume
116pub_type
杂志文章abstract:OBJECTIVE:Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situati...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00191-6
更新日期:1998-12-01 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::The intrinsic ability of resistance arteries to respond to transmural pressure is the single most important determinant of their function. Despite an ever-growing catalogue of signalling pathways that underlie the myogenic response, it remains an enigmatic mechanism. The myogenic response's mechanistic diversity has l...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs345
更新日期:2013-03-01 00:00:00
abstract::We studied the effects of intracoronary vasopressin on the relationship between pressure and flow in the coronary circulation of anaesthetised swine. In addition to measurements at control levels, diastolic pressure-flow relationships were constructed from steady-state points below a coronary pressure of 50 mmHg, wher...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.7.433
更新日期:1985-07-01 00:00:00
abstract::The voltage- and rate-dependence of the depression of the maximum rate of depolarisation (Vmax) by therapeutic concentrations of flecainide and lorcainide were studied in guinea-pig ventricle by standard microelectrode techniques. At normal resting potentials the drugs produced only minor depression of Vmax in the abs...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.5.251
更新日期:1983-05-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the effects of a calcium antagonist (diltiazem) and a catecholamine (noradrenaline) on extracellular potassium accumulation during global ischaemia. METHODS:Extracellular potassium concentration ([K+]e) was measured during 30 min global ischaemia in the isolated rat heart using a v...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.11.1040
更新日期:1992-11-01 00:00:00
abstract:OBJECTIVE:Lipoprotein lipase (LPL) mediated hydrolysis of circulating triglyceride (TG)-rich lipoproteins provides the heart with fatty acids. The present study was designed to investigate the influence of circulating TG and their lipolysis in facilitating translocation of LPL from the underlying cardiomyocyte cell sur...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00469-3
更新日期:2003-09-01 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::An oscillatory current (Ios) can be recorded after depolarising clamps of a given amplitude and duration. To determine whether Ios depends on other currents activated during the clamp, the Ios was investigated in the absence and in the presence of 4-aminopyridine (4-AP) and cesium (Cs). The following results were obta...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.11.637
更新日期:1982-11-01 00:00:00
abstract::The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptor...
journal_title:Cardiovascular research
pub_type: 评论,杂志文章,评审
doi:10.1016/s0008-6363(99)00319-3
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS:Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.2.188
更新日期:1993-02-01 00:00:00
abstract::Numerous epidemiological studies documented an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and the extent of atherosclerotic disease. However, clinical interventions targeting HDL cholesterol failed to show clinical benefits with respect to cardiovascular risk reduction, sugge...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu136
更新日期:2014-08-01 00:00:00
abstract:Aims:Heart failure (HF) produces left atrial (LA)-selective fibrosis and promotes atrial fibrillation. HF also causes adrenergic activation, which contributes to remodelling via a variety of signalling molecules, including the exchange protein activated by cAMP (Epac). Here, we evaluate the effects of Epac1-signalling ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy173
更新日期:2019-01-01 00:00:00
abstract::The rate of QT adaptation to abrupt changes in pacing rate was studied in seven patients with newly diagnosed complete heart block with a ventricular escape rate of less than 40 beats.min-1. Their median age was 70 (range 36-84) years, and none was taking any cardioactive medication known to affect the QT interval. Fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.1.67
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00311-4
更新日期:2001-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to compare platelet function in diabetic and non-diabetic survivors of acute myocardial infarction and to relate it to an index of free radical activity in these patients. DESIGN:In vivo and in vitro indices of platelet function and diene conjugate molar ratios were measured in diabetic and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.8.676
更新日期:1991-08-01 00:00:00
abstract:OBJECTIVE:To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS:A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of tra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00273-5
更新日期:2001-07-01 00:00:00
abstract:AIMS:Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with aging in HFrEF potentially leading to targeted therapies in this vulnerable...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa279
更新日期:2020-10-01 00:00:00
abstract::Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Precon...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.01.012
更新日期:2006-05-01 00:00:00
abstract::The development of the heart is a complex process during which different cell types progressively contribute to shape a four-chambered pumping organ. Over the last decades, our understanding of the specification and transcriptional regulation of cardiac development has been greatly augmented as has our understanding o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr078
更新日期:2011-07-15 00:00:00
abstract:Aims:Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate inflammatory pathways and are involved in cardiovascular disease. We aimed to screen and validate circulating microRNAs correlated with atherosclerosis development in humans, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx157
更新日期:2017-11-01 00:00:00
abstract:AIMS:Disturbed blood flow at arterial branches and curvatures modulates endothelial function and predisposes the region to endothelial inflammation and subsequent development of atherosclerotic lesions. Activation of the endothelial Toll-like receptors (TLRs), in particular TLR4, contributes to vascular inflammation. T...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz046
更新日期:2020-01-01 00:00:00
abstract::Eighty-one consecutive patients representing a wide clinical spectrum were studied to assess the degree of limitation of the atrial extrastimulus technique for measurement of atrioventricular node refractoriness; and, to determine the relationship between conductivity and functional refractoriness of the atrioventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.8.457
更新日期:1982-08-01 00:00:00
abstract:OBJECTIVE:Insulin protects cardiomyocytes from apoptosis. Insulin resistance usually refers to a defect in the ability of insulin to stimulate glucose uptake. It is unknown, however, whether or not insulin resistance compromises the cell-protective effect of the hormone. Caspases are a family of cysteine proteases that...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.012
更新日期:2007-12-01 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::The effects of both gradual and abrupt coronary occlusion on regional wall function (sonomicrometry) and left ventricular relaxation were studied in the intact dog heart. The ischaemic dysfunction observed in the two interventions as assessed by pressure-length loops showed considerably different patterns. The regiona...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.7.507
更新日期:1987-07-01 00:00:00
abstract:OBJECTIVES:Thrombin induces endothelial barrier failure by activating the contractile machinery of endothelial cells. Contractile activation is due to an increase in myosin light chain (MLC) phosphorylation. Here, it was investigated whether stimulation of endothelial cells with ATP can interrupt this thrombin-induced ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00427-9
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVES:I(Ks), the slow component of the delayed rectifier potassium current, underlies a strong beta-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I(Ks). Recent work has pointed to an opposing biological effect of beta(1)- and beta(3)-adrenoceptors in the heart....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00601-6
更新日期:2002-12-01 00:00:00
abstract:OBJECTIVE:Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents. METHODS:In phenobarbital-anaesthetised rats hypotension was induced b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00194-7
更新日期:1999-10-01 00:00:00
abstract::The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved an...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00293-9
更新日期:1998-03-01 00:00:00