CTLA4-IgG ameliorates homocysteine-accelerated atherosclerosis by inhibiting T-cell overactivation in apoE(-/-) mice.

Abstract:

AIMS:Cytotoxic T lymphocyte antigen 4 (CTLA4) exerts inhibitory effects on T-cell activation by competition with CD28. In this study, we investigated the effect of CTLA4-IgG on homocysteine (Hcy)-induced T-cell activation and potential signal pathways involved in atherosclerotic formation. METHODS AND RESULTS:The CD28 signal was significantly amplified by Hcy treatment in splenic T cells and hyperhomocysteinaemia (HHcy)-accelerated plaques in apolipoprotein E-deficient (apoE(-/-)) mice. As a major competitor of CD28, CTLA4-IgG (abatacept) pretreatment, 100 μg/week, in apoE(-/-) mice could reverse 2- and 4-week HHcy-accelerated atherosclerosis. Furthermore, the membrane level of CTLA4 was decreased and the endocytosis level was increased by HHcy. Endocytosed CTLA4 molecules by Hcy were in large vesicles, colocalized with lysosomes and endosomes. Hcy-increased CTLA4 endocytosis and secretion of inflammatory cytokines in T cells were blocked by CTLA4-IgG and the PI3K inhibitor LY294002. Blocking the CD28 signal pathway in T cells significantly decreased Hcy-promoted macrophage migration. CONCLUSION:These results illustrate a novel mechanism of CD28-dependent T-cell costimulation involved in HHcy-accelerated atherosclerosis, which extends the pharmacological application of CTLA4-IgG for atherosclerosis.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Ma K,Lv S,Liu B,Liu Z,Luo Y,Kong W,Xu Q,Feng J,Wang X

doi

10.1093/cvr/cvs330

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

349-59

issue

2

eissn

0008-6363

issn

1755-3245

pii

cvs330

journal_volume

97

pub_type

杂志文章
  • A new rat model of diabetic macrovascular complication.

    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

    authors: Bouvet C,Peeters W,Moreau S,DeBlois D,Moreau P

    更新日期:2007-02-01 00:00:00

  • Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium.

    abstract:OBJECTIVE:In human heart failure beta-adrenergic-mediated protein kinase A (PKA) activity is down-regulated, while protein kinase C (PKC) activity is up-regulated. PKC-mediated myofilament protein phosphorylation might be detrimental for contractile function in cardiomyopathy. This study was designed to reveal the effe...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2005.11.021

    authors: van der Velden J,Narolska NA,Lamberts RR,Boontje NM,Borbély A,Zaremba R,Bronzwaer JG,Papp Z,Jaquet K,Paulus WJ,Stienen GJ

    更新日期:2006-03-01 00:00:00

  • Echocardiographic determination of stroke volume during rapid atrial pacing and volume loading in normal rats.

    abstract:OBJECTIVE:The aim was to validate echocardiographic assessment of acute changes of left ventricular stroke volume in normal rats. METHODS:By transthoracic use of a 7.5 MHz ultrasonic transducer, the left ventricular dimensions were determined before and during rapid atrial pacing and saline infusion in seven Wistar ra...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/26.8.765

    authors: Nakamura T,Matsumuro A,Kuribayashi T,Matsubara K,Shima M,Shimoo K,Katsume H,Nakagawa M

    更新日期:1992-08-01 00:00:00

  • Ventricular expression of brain natriuretic peptide gene following orthotopic cardiac transplantation in children--a three year follow up.

    abstract:OBJECTIVE:The aim was to examine ventricular brain natriuretic peptide (B-type natriuretic peptide, BNP) gene expression and to determine its relationship with ventricular BNP and circulating BNP levels in paediatric cardiac transplant recipients, over a three year period after transplantation. METHODS:Total RNA extra...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.12.2135

    authors: Ationu A,Sorensen K,Whitehead B,Singer D,Burch M,Carter ND

    更新日期:1993-12-01 00:00:00

  • Apoptosis induction by nitric oxide in adult cardiomyocytes via cGMP-signaling and its impairment after simulated ischemia.

    abstract:OBJECTIVE:Nitric oxide (NO) has been shown to induce apoptosis in cardiomyocytes under normoxic conditions. The ability of NO to induce apoptosis after ischemia-reperfusion, a situation of increased NO release in vivo, has not been investigated. The present study was undertaken to characterize the pathway of induction ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(99)00272-2

    authors: Taimor G,Hofstaetter B,Piper HM

    更新日期:2000-02-01 00:00:00

  • Characterization of complex heart rate dynamics and their pharmacological disorders by non-linear prediction and special data transformations.

    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:

    authors: Hoyer D,Schmidt K,Zwiener U,Bauer R

    更新日期:1996-03-01 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

  • The renin-angiotensin system, dietary salt, and increased sensitivity to noradrenaline in mesenteric vasculature preparations from renal/salt hypertensive rats.

    abstract::Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Di...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/10.2.232

    authors: Collis MG,Alps BJ

    更新日期:1976-03-01 00:00:00

  • Vascular effects of loop diuretics.

    abstract::Although it is generally believed that the beneficial effect of loop diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vitro and in vivo experiments, has accumulated showing that administration of furosemide causes direct vascular effects, which probably contribut...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(96)00134-4

    authors: Dormans TP,Pickkers P,Russel FG,Smits P

    更新日期:1996-12-01 00:00:00

  • Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

    abstract::Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/20.10.721

    authors: Puddu PE,Jouve R,Langlet F,Guillen JC,Fornaris M,Torresani J,Reale A

    更新日期:1986-10-01 00:00:00

  • Emerging role of G protein-coupled receptors in microvascular myogenic tone.

    abstract::Blood flow autoregulation results from the ability of resistance arteries to reduce or increase their diameters in response to changes in intravascular pressure. The mechanism by which arteries maintain a constant blood flow to organs over a range of pressures relies on this myogenic response, which defines the intrin...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvs152

    authors: Kauffenstein G,Laher I,Matrougui K,Guérineau NC,Henrion D

    更新日期:2012-07-15 00:00:00

  • Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of blood pressure control.

    abstract:OBJECTIVE:Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neu...

    journal_title:Cardiovascular research

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0008-6363(01)00325-x

    authors: Lepori M,Sartori C,Duplain H,Nicod P,Scherrer U

    更新日期:2001-09-01 00:00:00

  • PPARdelta and PGC1alpha act cooperatively to induce haem oxygenase-1 and enhance vascular endothelial cell resistance to stress.

    abstract:AIMS:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcriptional regulators. PPARdelta has an established role in metabolism, wound healing, and angiogenesis. However, little is known about its function in endothelial homeostasis. We investigat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp365

    authors: Ali F,Ali NS,Bauer A,Boyle JJ,Hamdulay SS,Haskard DO,Randi AM,Mason JC

    更新日期:2010-03-01 00:00:00

  • Do statins have an antiarrhythmic activity?

    abstract::Sudden cardiac death, which is mainly associated with the presence of life-threatening ventricular arrhythmias, is a common 'killer' among patients with coronary artery disease. Moreover, atrial fibrillation is the most common arrhythmia encountered in the clinical practice. The beneficial effect of statins on cardiov...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2007.02.029

    authors: Kostapanos MS,Liberopoulos EN,Goudevenos JA,Mikhailidis DP,Elisaf MS

    更新日期:2007-07-01 00:00:00

  • Is angiotensin II a proliferative factor of cardiac fibroblasts?

    abstract::Angiotensin II has been implicated as an important factor in cardiac remodeling, particularly in the development of pathological left ventricular hypertrophy. It is generally assumed that angiotensin II is able to alter the phenotype of cardiac myocytes and fibroblasts, and several experiments have suggested that this...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(01)00448-5

    authors: Bouzegrhane F,Thibault G

    更新日期:2002-02-01 00:00:00

  • Effects of long term treatment with an alpha 1 adrenoceptor blocker on cardiac hypertrophy, contractility, and myosin isoenzymes in spontaneously hypertensive rats.

    abstract:STUDY OBJECTIVE:The aim was to investigate the effects of long-term treatment with an alpha 1 blocker, bunazosin hydrochloride, on blood pressure, heart weight, myocardial contractility, and ventricular myosin isoenzyme pattern in spontaneously hypertensive rats (SHR). DESIGN:Bunazosin hydrochloride was given orally i...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.7.565

    authors: Takeda N,Nakamura I,Ohkubo T,Iwai T,Tanamura A,Nagano M

    更新日期:1991-07-01 00:00:00

  • Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization.

    abstract:AIMS:To determine the role of gap junctions (GJs) in hypoxic pulmonary vasoconstriction (HPV). METHODS AND RESULTS:Studies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F2α...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt129

    authors: Kizub IV,Strielkov IV,Shaifta Y,Becker S,Prieto-Lloret J,Snetkov VA,Soloviev AI,Aaronson PI,Ward JP

    更新日期:2013-08-01 00:00:00

  • The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF.

    abstract:BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00320-5

    authors: Derakhchan K,Villemaire C,Talajic M,Nattel S

    更新日期:2001-04-01 00:00:00

  • Frontiers in positron emission tomography imaging of the vulnerable atherosclerotic plaque.

    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

    authors: MacAskill MG,Newby DE,Tavares AAS

    更新日期:2019-12-01 00:00:00

  • Interferon-gamma and atherosclerosis: pro- or anti-atherogenic?

    abstract::Atherosclerosis is considered to be a form of chronic inflammation governed by a complex network of inter- and intra-cellular signaling pathways. The pleiotropic cytokine interferon-gamma (IFN-gamma) is a key pro-inflammatory mediator that is expressed at high levels in atherosclerotic lesions. IFN-gamma regulates the...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2005.04.019

    authors: Harvey EJ,Ramji DP

    更新日期:2005-07-01 00:00:00

  • Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes: evidence of A3 receptor involvement.

    abstract:OBJECTIVE:The aim was to further characterise an experimental model of preconditioning of isolated rabbit cardiomyocytes and to determine the role of adenosine receptor subtypes in initiation of the protective response. METHODS:Isolated myocytes were subjected to 5 min preincubation in the presence or absence of gluco...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/28.7.1049

    authors: Armstrong S,Ganote CE

    更新日期:1994-07-01 00:00:00

  • Transcriptome and proteome mapping in the sheep atria reveal molecular features of atrial fibrillation progression.

    abstract:AIMS:Atrial fibrillation (AF) is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing th...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvaa307

    authors: Alvarez-Franco A,Rouco R,Ramirez RJ,Guerrero-Serna G,Tiana M,Cogliati S,Kaur K,Saeed M,Magni R,Enriquez JA,Sanchez-Cabo F,Jalife J,Manzanares M

    更新日期:2020-10-29 00:00:00

  • Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity.

    abstract::Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.1.37

    authors: Hind CR,Griffin JF,Pack S,Latchman YE,Drake HF,Jones HM,Brostoff J,Dormandy TL,Treasures T

    更新日期:1988-01-01 00:00:00

  • Combined therapy with PPARalpha agonist and L-carnitine rescues lipotoxic cardiomyopathy due to systemic carnitine deficiency.

    abstract:OBJECTIVE:Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily and are key regulators of fatty acid oxidation (FAO) in the heart. Systemic carnitine deficiency (SCD) causes disorders of FAO and induces hypertrophic cardiomy...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.02.005

    authors: Asai T,Okumura K,Takahashi R,Matsui H,Numaguchi Y,Murakami H,Murakami R,Murohara T

    更新日期:2006-06-01 00:00:00

  • Effect of increases in afterload before and after coronary occlusion in awake dogs.

    abstract::Ventricular function curves relating stroke work and left ventricular end-diastolic pressure were generated in awake dogs during increases in preload produced by infusion of fluid and during increases in afterload produced by administration of phenylephrine. The ventricular function curves produced by preloading were ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.7.392

    authors: Rosenfeldt FL,Cobb FR,Bache RJ,Sabiston DC Jr

    更新日期:1979-07-01 00:00:00

  • Peripheral blood flow and noradrenaline responsiveness: the effect of physiological hyperinsulinemia.

    abstract:OBJECTIVE:Insulin seems to have vasodilator properties, but it is unclear if insulin in postprandial concentrations is a specific vasodilator of skeletal muscle resistance arterioles only or that various types of vessels are affected. The aim of the present study was to determine the direct effects and the time course ...

    journal_title:Cardiovascular research

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0008-6363(97)00035-7

    authors: de Haan CH,van Dielen FM,Houben AJ,de Leeuw PW,Huvers FC,De Mey JG,Wolffenbuttel BH,Schaper NC

    更新日期:1997-04-01 00:00:00

  • Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCalpha.

    abstract:OBJECTIVE:Oxidized low-density lipoprotein (ox-LDL) increases superoxide anion (O(2)(-)) production by the endothelial nitric oxide (NO) synthase (eNOS). We assessed whether the uncoupling of eNOS was associated with alterations in eNOS phosphorylation and/or the assembly of the eNOS signaling complex. METHODS AND RES...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2004.11.003

    authors: Fleming I,Mohamed A,Galle J,Turchanowa L,Brandes RP,Fisslthaler B,Busse R

    更新日期:2005-03-01 00:00:00

  • Left ventricular dysfunction of isolated working rat hearts after chronic alcohol consumption.

    abstract::The mechanical, haemodynamic, and energetic functions of isolated perfused working hearts from chronic alcoholic and control rats were studied. Male Long-Evans rats were fed a nutritionally-complete liquid diet containing 38% of daily calories as ethanol (isocaloric replacement with dextrin-maltose for controls) for 3...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.3.136

    authors: Segel LD,Rendig SV,Mason DT

    更新日期:1979-03-01 00:00:00

  • Polymorphic ventricular tachycardias induced by D-sotalol and phenylephrine in canine preparations of atrioventricular block: initiation in the conduction system followed by spatially unstable re-entry.

    abstract:OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(98)00036-4

    authors: Derakhchan K,Cardinal R,Brunet S,Klug D,Pharand C,Kuś T,Sasyniuk BI

    更新日期:1998-06-01 00:00:00

  • Effect of exercise training on the ability of the rat heart to tolerate hydrogen peroxide.

    abstract:OBJECTIVE:The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H(2)O(2))-induced damage. METHODS:Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min/day, 22 m/min, 6 degrees grade, 5 days/week). Isolated perfused working hearts from ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(03)00285-2

    authors: Taylor RP,Ciccolo JT,Starnes JW

    更新日期:2003-06-01 00:00:00