Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate.

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 TLR2-transfected human embryonic kidney 293 cells and human monocytes, oxidized low-density lipoproteins inhibited nuclear factor (NF)-kappaB-driven transcriptional activity and chemokine gene expression in response to TLR2 ligands. Sphingosine 1-phosphate (S1P) and oxidized palmitoyl-arachidonoyl-phosphatidylcholine, but not lipoprotein-carried lysophospholipids, inhibited TLR2 activation. Silencing experiments in TLR2-transfected 293 cells showed that the S1P-mediated attenuation effect is mediated by S1P receptors type 1 and type 2. To address the physiological significance of these findings, additional experiments were performed in human peripheral blood monocytes and monocyte-derived macrophages. In both cell types, S1P selectively attenuated TLR2 signalling, as NF-kappaB and extracellular signal-regulated kinase activation, but not c-Jun amino terminal kinase phosphorylation, were inhibited by physiologically relevant concentrations of S1P. Moreover, the attenuation of TLR2 signalling was partially reverted by pharmacological inhibition of phosphoinositide 3-kinase (PI3K) and Ras pathways. In addition, S1P inhibited the chemokine gene expression elicited by TLR2, but not by TLR4 ligands. CONCLUSION:These findings disclose a cross-talk mechanism between lipoprotein components and TLR in which engagement of S1P receptors exert selective attenuation of TLR2-dependent activation via PI3K and Ras signalling. A corollary to these data is that the negative cross-talk of S1P receptors and TLR2 signalling might be involved in the atheroprotective effects of S1P.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Dueñas AI,Aceves M,Fernández-Pisonero I,Gómez C,Orduña A,Crespo MS,García-Rodríguez C

doi

10.1093/cvr/cvn087

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

537-44

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvn087

journal_volume

79

pub_type

杂志文章
  • Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.

    abstract::Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,meta分析

    doi:10.1093/cvr/cvy145

    authors: Panahi M,Papanikolaou A,Torabi A,Zhang JG,Khan H,Vazir A,Hasham MG,Cleland JGF,Rosenthal NA,Harding SE,Sattler S

    更新日期:2018-09-01 00:00:00

  • Cardiac protection by ischaemic preconditioning is not mediated by myocardial stunning.

    abstract:OBJECTIVE:Previous studies have shown that cardiac protection by ischaemic preconditioning wanes before contractile function recovers; thus stunning is insufficient to cause preconditioning. To test whether reduced contractile effort is necessary for preconditioning induced protection, the effect on myocardial infarct ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.4.585

    authors: Matsuda M,Catena TG,Vander Heide RS,Jennings RB,Reimer KA

    更新日期:1993-04-01 00:00:00

  • The effect of therapeutic doses of lidocaine hydrochloride on the effective refractory period of the right ventricle in man.

    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

    authors: Olsson SB,Harper R,Rydén L,Hilmy WA

    更新日期:1975-09-01 00:00:00

  • Oestrogen enhances cardiotoxicity induced by Sunitinib by regulation of drug transport and metabolism.

    abstract:AIMS:To define the molecular mechanisms of cardiotoxicity induced by Sunitinib and to identify the role of biological sex in modulating toxicity. METHODS AND RESULTS:Exposure of isolated cardiomyocytes to plasma-relevant concentrations of Sunitinib and other tyrosine kinase inhibitors produces a broad spectrum of abno...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvv152

    authors: Harvey PA,Leinwand LA

    更新日期:2015-07-01 00:00:00

  • Mechanical properties and structure of carotid arteries in mice lacking desmin.

    abstract:OBJECTIVE:Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS:To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves o...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(01)00278-4

    authors: Lacolley P,Challande P,Boumaza S,Cohuet G,Laurent S,Boutouyrie P,Grimaud JA,Paulin D,Lamazière JM,Li Z

    更新日期:2001-07-01 00:00:00

  • Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

    abstract:AIMS:Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. METHODS AND RESULT...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvy257

    authors: Røe ÅT,Ruud M,Espe EK,Manfra O,Longobardi S,Aronsen JM,Nordén ES,Husebye T,Kolstad TRS,Cataliotti A,Christensen G,Sejersted OM,Niederer SA,Andersen GØ,Sjaastad I,Louch WE

    更新日期:2019-03-15 00:00:00

  • Noninvasively and invasively measured pulsatile haemodynamics with graded arterial stenosis.

    abstract::Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respe...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.1.45

    authors: Farrar DJ,Green HD,Peterson DW

    更新日期:1979-01-01 00:00:00

  • Angiotensin II, adhesion, and cardiac fibrosis.

    abstract::Angiotensin II (AII) plays a critical role in cardiac remodeling. This peptide promotes cardiac myocyte hypertrophy and cardiac fibroblast interstitial fibrotic changes associated with left ventricular hypertrophy, post myocardial infarction remodeling and congestive heart failure. AII mediates cardiac myocyte hypertr...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(00)00044-4

    authors: Schnee JM,Hsueh WA

    更新日期:2000-05-01 00:00:00

  • Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains.

    abstract:AIMS:Apolipoprotein E (apoE) may act as a vasculoprotective factor by promoting plasma lipid clearance and cholesterol efflux. Moreover, apoE accumulates at sites of vascular injury and modulates the effect of growth factors on smooth muscle cells (SMCs). Experimental data suggested that hypothalamic apoE expression is...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt126

    authors: Schroeter MR,Leifheit-Nestler M,Hubert A,Schumann B,Glückermann R,Eschholz N,Krüger N,Lutz S,Hasenfuss G,Konstantinides S,Schäfer K

    更新日期:2013-08-01 00:00:00

  • Structure and reactivity of small arteries in aging.

    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

    authors: Moreau P,d'Uscio LV,Lüscher TF

    更新日期:1998-01-01 00:00:00

  • Developmental changes in myocardial contractile responses to inotropic agents.

    abstract::Although substantial information has accumulated over the past decade, many gaps remain in our understanding of the regulation of contractility and modulation of inotropic responsiveness in the developing heart. There are several important problems facing investigators in the field of developmental cardiology. Respons...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/26.1.3

    authors: Artman M

    更新日期:1992-01-01 00:00:00

  • Endocardial injury and the pathogenesis of mural thrombosis in the left ventricle.

    abstract::To define the interactions between blood and endocardium damaged by lactic acid, the left ventricles of 48 isolated continuously perfused and beating hearts were exposed for 0-4 hours to Krebs Henseleit buffer (KHB) with or without 33 mumol.ml-1 of lactic acid (pH 6.4). After excising its apex, the left ventricle was ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/23.6.478

    authors: Carter G,Gavin JB

    更新日期:1989-06-01 00:00:00

  • Tubulin polymerization modifies cardiac sodium channel expression and gating.

    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

    authors: Casini S,Tan HL,Demirayak I,Remme CA,Amin AS,Scicluna BP,Chatyan H,Ruijter JM,Bezzina CR,van Ginneken AC,Veldkamp MW

    更新日期:2010-03-01 00:00:00

  • Role of microRNAs in the reperfused myocardium towards post-infarct remodelling.

    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

    authors: Zhu H,Fan GC

    更新日期:2012-05-01 00:00:00

  • Progressive reduction in norepinephrine overflow during cardiac sympathetic nerve stimulation in the anaesthetized dog.

    abstract::The left ansa subclavia was stimulated at supramaximal intensity at a frequency of Hz in open-chest, anaesthetized dogs for periods of about 10 min. Arterial blood pressure, myocardial contractile force, and coronary sinus blood flow reached peak values after 1 or 2 min of stimulation, and then declined gradually thro...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/10.5.549

    authors: Levy MN,Blattberg B

    更新日期:1976-09-01 00:00:00

  • Electrical conductance of mouse connexin45 gap junction channels is modulated by phosphorylation.

    abstract::In this study we report about the modulation of connexin45 (Cx45) gap junction channel properties by phosphorylation of the connexin molecules through different protein kinases. Phosphorylation of Cx45 was studied in HeLa cells transfected with mouse Cx45 (mCx45). Using Western blotting (WB) and immunocytochemistry, t...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00047-x

    authors: van Veen TA,van Rijen HV,Jongsma HJ

    更新日期:2000-06-01 00:00:00

  • GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy.

    abstract:AIMS:GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs001

    authors: Han M,Yang Z,Sayed D,He M,Gao S,Lin L,Yoon S,Abdellatif M

    更新日期:2012-03-15 00:00:00

  • Phosphodiesterase 5 inhibitors: are they cardioprotective?

    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

    authors: Reffelmann T,Kloner RA

    更新日期:2009-07-15 00:00:00

  • Human Influenza A virus causes myocardial and cardiac-specific conduction system infection associated with early inflammation and premature death.

    abstract:AIMS:Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capac...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvaa117

    authors: Filgueiras-Rama D,Vasilijevic J,Jalife J,Noujaim SF,Alfonso JM,Nicolas-Avila JA,Gutierrez C,Zamarreño N,Hidalgo A,Bernabé A,Cop CP,Ponce-Balbuena D,Guerrero-Serna G,Calle D,Desco M,Ruiz-Cabello J,Nieto A,Falcon A

    更新日期:2020-04-28 00:00:00

  • Adrenomedullin induces lymphangiogenesis and ameliorates secondary lymphoedema.

    abstract:AIMS:Adrenomedullin (AM) is a multifunctional peptide hormone that plays a significant role in vasodilation and angiogenesis. Lymphoedema is a common but refractory disorder that is difficult to be treated with conventional therapy. We therefore investigated whether AM promotes lymphangiogenesis and improves lymphoedem...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn228

    authors: Jin D,Harada K,Ohnishi S,Yamahara K,Kangawa K,Nagaya N

    更新日期:2008-12-01 00:00:00

  • Does nitric oxide modulate cardiac ryanodine receptor function? Implications for excitation-contraction coupling.

    abstract::Nitric oxide (NO) is a highly reactive, free radical signalling molecule that is constitutively released in cardiomyocytes by both the endothelial and neuronal isoforms of nitric oxide synthase (eNOS and nNOS, respectively). There are increasing data indicating that NO modulates various proteins involved in excitation...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvm012

    authors: Lim G,Venetucci L,Eisner DA,Casadei B

    更新日期:2008-01-15 00:00:00

  • Characterization of excitation-contraction coupling in conscious dogs with pacing-induced heart failure.

    abstract:OBJECTIVE:In isolated cardiac preparations of non-failing hearts from different species, including man, there is a positive force-frequency relation which is reversed into a negative relation in preparation from failing hearts. Whether or not such relations between ventricular function and heart rate hold true in the i...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(97)00246-0

    authors: Neumann T,Ravens U,Heusch G

    更新日期:1998-02-01 00:00:00

  • Reverse rate dependency is an intrinsic property of canine cardiac preparations.

    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

    authors: Bányász T,Horváth B,Virág L,Bárándi L,Szentandrássy N,Harmati G,Magyar J,Marangoni S,Zaza A,Varró A,Nánási PP

    更新日期:2009-11-01 00:00:00

  • Unfavourable consequences of chronic cardiac HIF-1α stabilization.

    abstract:AIMS:The hypoxia-inducible factor-1 (HIF-1) is the master modulator of hypoxic gene expression. The effects of chronically stabilized cardiac HIF-1α and its role in the diseased heart are not precisely known. The aims of this study were as follows: (i) to elucidate consequences of HIF-1α stabilization in the heart; (ii...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs014

    authors: Hölscher M,Schäfer K,Krull S,Farhat K,Hesse A,Silter M,Lin Y,Pichler BJ,Thistlethwaite P,El-Armouche A,Maier LS,Katschinski DM,Zieseniss A

    更新日期:2012-04-01 00:00:00

  • TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension.

    abstract:AIMS:Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt067

    authors: Basu R,Lee J,Morton JS,Takawale A,Fan D,Kandalam V,Wang X,Davidge ST,Kassiri Z

    更新日期:2013-06-01 00:00:00

  • Single bolus administration of recombinant tissue plasminogen activator: effects on infarct related vessel patency, microvascular perfusion, and microvascular reocclusion in a canine model of thrombotic occlusion/reperfusion.

    abstract:STUDY OBJECTIVE:The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. DESIGN:Coronary arterial thrombi were induced by a copper coi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.3.184

    authors: Longridge DJ,Follenfant MJ,Ford AJ

    更新日期:1991-03-01 00:00:00

  • Chronic beta2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism.

    abstract:OBJECTIVE:The aim of this study was to determine whether chronic beta-adrenergic receptor (beta-AR) stimulation induces proliferation of human cardiac fibroblasts and to investigate the mechanism(s) involved. METHODS AND RESULTS:In vitro cultures of human cardiac fibroblasts were established from biopsies of right atr...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00729-0

    authors: Turner NA,Porter KE,Smith WH,White HL,Ball SG,Balmforth AJ

    更新日期:2003-03-01 00:00:00

  • Augmentation of late sodium current unmasks the proarrhythmic effects of amiodarone.

    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

    authors: Wu L,Rajamani S,Shryock JC,Li H,Ruskin J,Antzelevitch C,Belardinelli L

    更新日期:2008-02-01 00:00:00

  • Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart.

    abstract:OBJECTIVES:Diastolic dysfunction that determines symptoms and prognosis in patients with systolic dysfunction causes heart failure even in the absence of systolic dysfunction. Our recent studies have suggested that myocardial stiffening is likely to play a crucial role in triggering deleterious cardiac disorder. This s...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00341-3

    authors: Yamamoto K,Masuyama T,Sakata Y,Nishikawa N,Mano T,Yoshida J,Miwa T,Sugawara M,Yamaguchi Y,Ookawara T,Suzuki K,Hori M

    更新日期:2002-07-01 00:00:00

  • Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure.

    abstract::Congestive heart failure may be deemed the epidemic of cardiology in the 21st century in the industrialized part of the world. Although new therapies improving morbidity and mortality from chronic heart failure have emerged it is likely that there is a growing role for digoxin. Thus, digoxin treatment is known to cont...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(02)00466-2

    authors: Kjeldsen K,Nørgaard A,Gheorghiade M

    更新日期:2002-09-01 00:00:00