Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice.

Abstract:

AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. METHODS AND RESULTS:We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47(phox) and p67(phox) through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. CONCLUSION:Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Liu SL,Li YH,Shi GY,Tang SH,Jiang SJ,Huang CW,Liu PY,Hong JS,Wu HL

doi

10.1093/cvr/cvp043

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

161-9

issue

1

eissn

0008-6363

issn

1755-3245

pii

cvp043

journal_volume

82

pub_type

杂志文章
  • Impaired local regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation.

    abstract:AIMS:Altered Ca(2+) handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities in protein phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into the local, rather than global, regulation of PP...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu123

    authors: Chiang DY,Li N,Wang Q,Alsina KM,Quick AP,Reynolds JO,Wang G,Skapura D,Voigt N,Dobrev D,Wehrens XH

    更新日期:2014-07-01 00:00:00

  • Poly(ADP-ribose) polymerase-2 depletion reduces doxorubicin-induced damage through SIRT1 induction.

    abstract:AIMS:Doxorubicin (DOX) is widely used in cytostatic treatments, although it may cause cardiovascular dysfunction as a side effect. DOX treatment leads to enhanced free radical production that in turn causes DNA strand breakage culminating in poly(ADP-ribose) polymerase (PARP) activation and mitochondrial and cellular d...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvr246

    authors: Szántó M,Rutkai I,Hegedus C,Czikora Á,Rózsahegyi M,Kiss B,Virág L,Gergely P,Tóth A,Bai P

    更新日期:2011-12-01 00:00:00

  • Doppler blood velocity in the pulmonary artery of infants, children, and adults.

    abstract::A pulsed, range gated, directional, ultrasonic, Doppler blood velocity meter was used to record signals from the pulmonary artery in 52 normal subjects ranging in age from less than 1 week to over 30 years. Signals were obtained from an unfocused transducer in the second or third left intercostal space using a 2.25 MH...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/20.11.816

    authors: Targett RC,Heldt GP,McIlroy MB

    更新日期:1986-11-01 00:00:00

  • Serotonin receptor blockade improves distal perfusion after lower limb ischemia in the fatty Zucker rat.

    abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00538-2

    authors: Janiak P,Lainée P,Grataloup Y,Luyt CE,Bidouard JP,Michel JB,O'Connor SE,Herbert JM

    更新日期:2002-11-01 00:00:00

  • Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists.

    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

    authors: Kameritsch P,Pogoda K,Ritter A,Münzing S,Pohl U

    更新日期:2012-03-01 00:00:00

  • Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function.

    abstract:OBJECTIVE:Current guidelines are controversial regarding exercise intensity in cardiovascular prevention and rehabilitation. Although high-intensity training induces larger increases in fitness and maximal oxygen uptake (VO(2max)), moderate intensity is often recommended as equally effective. Controlled preclinical stu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2005.03.010

    authors: Kemi OJ,Haram PM,Loennechen JP,Osnes JB,Skomedal T,Wisløff U,Ellingsen Ø

    更新日期:2005-07-01 00:00:00

  • A mechanism of ryanodine receptor modulation by FKBP12/12.6, protein kinase A, and K201.

    abstract:AIMS:Our objective was to explore the functional interdependence of protein kinase A (PKA) phosphorylation with binding of modulatory FK506 binding proteins (FKBP12/12.6) to the ryanodine receptor (RyR). RyR type 1 or type 2 was prepared from rabbit skeletal muscle or pig cardiac muscle, respectively. In heart failure,...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp273

    authors: Blayney LM,Jones JL,Griffiths J,Lai FA

    更新日期:2010-01-01 00:00:00

  • Effects of physical training on beta-adrenergic receptors in rat myocardial tissue.

    abstract::A diminished sympathetic activity has been related to training bradycardia seen at rest and during exercise. In order to evaluate if changes in heart adrenergic receptors can be one of the mechanisms by which the sympathetic responsiveness could be decreased by physical training, the number and affinity of beta-adrene...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/16.9.530

    authors: Sylvestre-Gervais L,Nadeau A,Nguyen MH,Tancrède G,Rousseau-Migneron S

    更新日期:1982-09-01 00:00:00

  • Strategies for directing the differentiation of stem cells into the cardiomyogenic lineage in vitro.

    abstract::Most studies on stem cell transplantation therapy on myocardially infarcted animal models and phase-I human clinical trials have focused on the use of undifferentiated stem cells. There is a strong possibility that some degree of cardiomyogenic differentiation of stem cells in vitro prior to transplantation would resu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2003.12.022

    authors: Heng BC,Haider HKh,Sim EK,Cao T,Ng SC

    更新日期:2004-04-01 00:00:00

  • Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat.

    abstract:OBJECTIVE:At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Brown LA,Nunez DJ,Brookes CI,Wilkins MR

    更新日期:1995-06-01 00:00:00

  • Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats.

    abstract:OBJECTIVE:This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia. METHODS:Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autor...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(97)00132-6

    authors: Avontuur JA,Bruining HA,Ince C

    更新日期:1997-08-01 00:00:00

  • Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat.

    abstract:OBJECTIVE:In menopause, aging and decreased estrogen levels are risk factors contributing to impaired vascular function. Previously, in a young ovariectomized rat model, we demonstrated an increase in prostaglandin H synthase (PGHS)-dependent vasoconstriction that could be prevented by estrogen replacement. Subsequentl...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2003.11.009

    authors: Armstrong SJ,Xu Y,Davidge ST

    更新日期:2004-02-01 00:00:00

  • Reversible activation of nuclear factor-kappaB in human end-stage heart failure after left ventricular mechanical support.

    abstract:OBJECTIVE:Left ventricular assist devices (LVAD) have been used to 'bridge' patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called 'reverse remodeling', the underlying biological mecha...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(01)00433-3

    authors: Grabellus F,Levkau B,Sokoll A,Welp H,Schmid C,Deng MC,Takeda A,Breithardt G,Baba HA

    更新日期:2002-01-01 00:00:00

  • Influence of training on myocardial responses of rats subjected to conditions of ischaemia and hypoxia.

    abstract::Physical training has been advocated to minimize the problems associated with coronary heart disease; however, the responsible mechanisms are obscure. Rats trained to run on a treadmill were subjected to acute conditions of hypoxia and myocardial ischaemia. Trained rats were better able to maintain a higher level of c...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/10.3.359

    authors: Carey RA,Tipton CM,Lund DR

    更新日期:1976-05-01 00:00:00

  • Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1.

    abstract:OBJECTIVE:We studied the effects of temporary myocardial ischemia and reperfusion on myocyte injury and ventricular remodelling in wildtype and intercellular adhesion molecule-1- (ICAM-1) deficient mice. METHODS:ICAM-1-/- and ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subsequent reperfusion for...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00261-3

    authors: Metzler B,Mair J,Lercher A,Schaber C,Hintringer F,Pachinger O,Xu Q

    更新日期:2001-02-01 00:00:00

  • Adventitial fibroblast reactive oxygen species as autacrine and paracrine mediators of remodeling: bellwether for vascular disease?

    abstract::The importance of the vascular adventitia is increasingly being recognized not only in vascular disease but also in normal maintenance and homeostasis of vessels. Activation of the adventitia and its resident fibrocytic cells in response to injury, stretch, cytokines, and hormones has been shown to stimulate different...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2007.06.016

    authors: Haurani MJ,Pagano PJ

    更新日期:2007-09-01 00:00:00

  • Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart.

    abstract:AIMS:The ventricular wall of the heart is composed of trabeculated and compact layers, which are separated by yet unknown processes during embryonic development. Here, we wanted to explore the role of Notch2 and Numb/Numblike for myocardial trabeculation and compaction. METHODS AND RESULTS:We found that Notch2 activit...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs250

    authors: Yang J,Bücker S,Jungblut B,Böttger T,Cinnamon Y,Tchorz J,Müller M,Bettler B,Harvey R,Sun QY,Schneider A,Braun T

    更新日期:2012-11-01 00:00:00

  • Ecstasy produces left ventricular dysfunction and oxidative stress in rats.

    abstract:AIMS:Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. METHODS AND RESULTS:Echocardiography and pressure-volume conductance catheters were us...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn129

    authors: Shenouda SK,Lord KC,McIlwain E,Lucchesi PA,Varner KJ

    更新日期:2008-09-01 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

  • Activation of vascular BK channels by docosahexaenoic acid is dependent on cytochrome P450 epoxygenase activity.

    abstract:AIMS:n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochr...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvq411

    authors: Wang RX,Chai Q,Lu T,Lee HC

    更新日期:2011-05-01 00:00:00

  • m-Calpain antagonizes RhoA overactivation and endothelial barrier dysfunction under disturbed shear conditions.

    abstract:AIMS:It has been reported that laminar shear flow (LF) improves barrier functions in vascular endothelial cells (ECs), whereas disturbed flow (DF) impairs the barrier. Our previous study showed that LF stimulus led to the activation of the cysteine protease, m-calpain, in ECs, which can influence RhoA activity. We hypo...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp311

    authors: Miyazaki T,Honda K,Ohata H

    更新日期:2010-02-01 00:00:00

  • Targeted invalidation of SR-B1 in macrophages reduces macrophage apoptosis and accelerates atherosclerosis.

    abstract:AIMS:SR-B1 is a cholesterol transporter that exerts anti-atherogenic properties in liver and peripheral tissues in mice. Bone marrow (BM) transfer studies suggested an atheroprotective role in cells of haematopoietic origin. Here, we addressed the specific contribution of SR-B1 in the monocyte/macrophage. METHODS AND ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz138

    authors: Galle-Treger L,Moreau M,Ballaire R,Poupel L,Huby T,Sasso E,Troise F,Poti F,Lesnik P,Le Goff W,Gautier EL,Huby T

    更新日期:2020-03-01 00:00:00

  • A model for acute haemodynamic studies in the ascending aorta in pigs.

    abstract::Since data on velocity fields in the ascending aorta downstream of normal aortic valves in pigs have not yet been obtained velocity profiles were visualised using a hot film anemometer needle probe before and after total cardiopulmonary bypass and cold cardioplegic arrest. Furthermore, measurements were made during in...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.7.464

    authors: Hasenkam JM,Ostergaard JH,Pedersen EM,Paulsen PK,Nygaard H,Schurizek BA,Johannsen G

    更新日期:1988-07-01 00:00:00

  • Interleukin 8 and cardiovascular disease.

    abstract::Since the establishment of the inflammatory basis of atherosclerosis, several pro- or anti-inflammatory agents have been examined as potential mediators of the biochemical pathways of lesion formation. Interleukin (IL)-8 was first characterized in 1987. Since then, knowledge regarding its role in leucocyte trafficking...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvp241

    authors: Apostolakis S,Vogiatzi K,Amanatidou V,Spandidos DA

    更新日期:2009-12-01 00:00:00

  • Controlled expression of cardiac-directed adenylylcyclase type VI provides increased contractile function.

    abstract:OBJECTIVE:We have previously shown that cardiac-directed expression of adenylycyclase type VI (AC(VI)) increases heart function in transgenic mice, and improves heart function and survival in murine cardiomyopathy. However, a potential problem of crossbreeding paradigms that use lines with two constitutively active tra...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00539-4

    authors: Gao MH,Bayat H,Roth DM,Yao Zhou J,Drumm J,Burhan J,Hammond HK

    更新日期:2002-11-01 00:00:00

  • The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP.

    abstract:AIMS:During restenosis, vascular smooth muscle cells (VSMCs) migrate from the vascular media to the developing neointima. Preventing VSMC migration is therefore a therapeutic target for restenosis. Drugs, such as prostacyclin analogues, that increase the intracellular concentration of cyclic adenosine monophosphate (cA...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvv176

    authors: McKean JS,Murray F,Gibson G,Shewan DA,Tucker SJ,Nixon GF

    更新日期:2015-09-01 00:00:00

  • Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane microdomains.

    abstract:AIMS:Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.1 and KCNE1....

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu250

    authors: Moreno C,de la Cruz A,Oliveras A,Kharche SR,Guizy M,Comes N,Starý T,Ronchi C,Rocchetti M,Baró I,Loussouarn G,Zaza A,Severi S,Felipe A,Valenzuela C

    更新日期:2015-02-01 00:00:00

  • The contribution of sleep to social inequalities in cardiovascular disorders: a multi-cohort study.

    abstract:AIMS:Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz267

    authors: Petrovic D,Haba-Rubio J,de Mestral Vargas C,Kelly-Irving M,Vineis P,Kivimäki M,Nyberg S,Gandini M,Bochud M,Vollenweider P,d'Errico A,Barros H,Fraga S,Goldberg M,Zins M,Steptoe A,Delpierre C,Heinzer R,Carmeli C,Chade

    更新日期:2020-07-01 00:00:00

  • Platelet-activating factor (PAF) does not affect diastolic function in isolated rat hearts.

    abstract::Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused r...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(95)00181-6

    authors: Muñoz HR,Evans RD,Marsch SC,Foëx P

    更新日期:1995-12-01 00:00:00

  • Pretreatment with the adenosine A1 selective agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), causes a sustained limitation of infarct size in rabbits.

    abstract:OBJECTIVE:The highly selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), has been shown to be as cardioprotective as ischaemic preconditioning when evaluated with an early staining method using tetrazolium. However, tetrazolium-positive tissue measured 3 h after reperfusion may still over...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.4.652

    authors: Tsuchida A,Liu GS,Wilborn WH,Downey JM

    更新日期:1993-04-01 00:00:00