Abstract:
Aims:The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arterial thrombus formation in vivo at different levels of oxLDL using endothelial-specific LOX-1 transgenic mice (LOX-1TG) and a photochemical injury thrombosis model of the carotid artery. Methods and results:In mice fed a normal chow diet, time to arterial occlusion was unexpectedly prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity in carotid arteries of LOX-1TG mice were reduced by half. This effect was mediated by activation of octamer transcription factor 1 (Oct-1) leading to upregulation of the mammalian deacetylase silent information regulator-two 1 (SIRT1) via binding to its promoter and subsequent inhibition of NF-κB signaling. In contrast, intravenous injection of oxLDL as well as high cholesterol diet for 6 weeks led to a switch from the Oct-1/SIRT1 signal transduction pathway to the ERK1/2 pathway and in turn to an enhanced thrombotic response with shortened occlusion time. Conclusions:Thus, LOX-1 differentially regulates thrombus formation in vivo depending on the degree of activation by oxLDL. At low oxLDL levels LOX-1 activates the protective Oct-1/SIRT1 pathway, while at higher levels of the lipoprotein switches to the thrombogenic ERK1/2 pathway. These findings may be important for arterial thrombus formation in ACS and suggest that SIRT1 may represent a novel therapeutic target in this context.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Akhmedov A,Camici GG,Reiner MF,Bonetti NR,Costantino S,Holy EW,Spescha RD,Stivala S,Schaub Clerigué A,Speer T,Breitenstein A,Manz J,Lohmann C,Paneni F,Beer JH,Lüscher TFdoi
10.1093/cvr/cvx015subject
Has Abstractpub_date
2017-04-01 00:00:00pages
498-507issue
5eissn
0008-6363issn
1755-3245pii
2983689journal_volume
113pub_type
杂志文章abstract::The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00086-9
更新日期:2000-08-18 00:00:00
abstract::The renin-angiotensin-aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension a...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00110-8
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVE:H(2)O(2) can contract many arteries, however the underlying mechanisms are not fully understood. This study aims to test whether H(2)O(2)-induced vasoconstriction could be functionally attributed to the activation of P(2)-purinoceptors in rat aorta and to explore its possible signaling mechanisms. METHODS:Is...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00123-1
更新日期:2000-08-18 00:00:00
abstract::To investigate cardiovascular changes in experimental acromegaly, a growth hormone-secreting tumour (MtT-W-15) was implanted in adult female rats. Somatic and tumour growth occurred steadily during the 8 week study period, as did an increase in serum growth hormone titre. Weight of left ventricle and right ventricle i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.5.270
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:The primary aim of this study was to investigate whether activation of Na influx via voltage-gated Na channels can elevate sub-sarcolemmal ('fuzzy-space') [Na] and transiently activate Na/K pump current (I(p)). METHODS AND RESULTS:Initially, Na/K pump activity was characterised in whole-cell voltage-clamped ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00645-4
更新日期:2003-03-15 00:00:00
abstract:AIM:Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be u...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv254
更新日期:2016-01-01 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::This review focuses on the genomic response following a preconditioning stimulus. Initial studies demonstrated that classical ischemic preconditioning mediated by cyclic episodes of short durations of reversible ischemia and reperfusion could result in the reprogramming of gene expression. Some of these genes are tran...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.02.023
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVE:Some neuropeptides have direct cardiac effects and also modulate the cardiac effects of catecholamines. Vasopressin is an abundantly available neuropeptide having well known interactions with catecholamines in vascular smooth muscle. The aim of this study was to determine the direct and modulatory effects of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.9.1624
更新日期:1993-09-01 00:00:00
abstract::Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.104
更新日期:1985-02-01 00:00:00
abstract:AIMS:Proliferation of mammalian cardiomyocytes stops during the first weeks after birth, preventing the heart from regenerating after injury. Recently, several studies have indicated that induction of cardiomyocyte proliferation can be utilized to regenerate the mammalian heart. Thus, it is important to identify novel ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp360
更新日期:2010-03-01 00:00:00
abstract::Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic car...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz162
更新日期:2019-12-01 00:00:00
abstract:AIMS:Although increased Na(+)/Ca(2+) exchanger 1 (NCX1) expression is observed during heart failure (HF), the pathological role of NCX1 during the progression of HF remains unclear. We examined alterations of NCX1 expression and activity in hearts after transverse aortic constriction (TAC) surgery and explored whether ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw113
更新日期:2016-09-01 00:00:00
abstract:AIMS:Despite the observation that ErbB2 regulates sensitivity of the heart to doxorubicin or ErbB2-targeted cancer therapies, mechanisms that regulate ErbB2 expression and activity have not been studied. Since isoproterenol up-regulates ErbB2 in kidney and salivary glands and β2AR and ErbB2 complex in brain and heart, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv274
更新日期:2016-03-01 00:00:00
abstract::Felodipine (4(2,3-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonyl pyridine)), a selective vasodilating anti-hypertensive drug, was used in the treatment of spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto rats (WKYs) from age 6 to 14 weeks, ie during the time of high blo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.528
更新日期:1985-09-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN:Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioliga...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.9.764
更新日期:1991-09-01 00:00:00
abstract:OBJECTIVE:The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. METHODS:After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract:AIMS:A robust inflammatory response to tissue injury is a necessary part of the repair process but the deposition of scar tissue is a direct downstream consequence of this response in many tissues including the heart. Adult zebrafish not only possess the capacity to regenerate lost cardiomyocytes but also to remodel an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz221
更新日期:2020-06-01 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:The mesenchymal cushions lining the early embryonic heart undergo complex remodelling to form the membranous ventricular septum as well as the atrioventricular and semilunar valves in later life. Disruption of this process underlies the most common congenital heart defects. Here, we identified a novel role for Sli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv040
更新日期:2015-04-01 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:AIMS:Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mech...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp213
更新日期:2009-11-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN:Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetis...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.5.353
更新日期:1991-05-01 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:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00144-3
更新日期:1999-09-01 00:00:00
abstract::In acute myocardial infarction (MI), reactive oxygen species (ROS) are generated in the ischaemic myocardium especially after reperfusion. ROS directly injure the cell membrane and cause cell death. However, ROS also stimulate signal transduction to elaborate inflammatory cytokines, e.g. tumour necrosis factor-alpha (...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn335
更新日期:2009-02-15 00:00:00
abstract:AIMS:Animal studies show that transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). This study investigated the role of TGF-β1 in human AF and the mechanism of atrial-selective fibrosis. METHODS AND RESULTS:Atrial specimens from 17 open heart surgery patients ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt074
更新日期:2013-09-01 00:00:00
abstract:OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.001
更新日期:2007-11-01 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:OBJECTIVE:To examine if adenosine prevents oxidant-induced mitochondrial dysfunction by producing nitric oxide (NO) in cardiomyocytes. METHODS AND RESULTS:Adenosine significantly enhanced the fluorescence of DAF-FM, a dye specific for NO, implying that adenosine induces synthesis of NO. Adenosine-induced NO production...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.004
更新日期:2005-03-01 00:00:00