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 Resjournal_title
Cardiovascular researchauthors
Liu SL,Li YH,Shi GY,Tang SH,Jiang SJ,Huang CW,Liu PY,Hong JS,Wu HLdoi
10.1093/cvr/cvp043subject
Has Abstractpub_date
2009-04-01 00:00:00pages
161-9issue
1eissn
0008-6363issn
1755-3245pii
cvp043journal_volume
82pub_type
杂志文章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
更新日期:2014-07-01 00:00:00
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
更新日期:2011-12-01 00:00:00
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
更新日期:1986-11-01 00:00:00
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
更新日期:2002-11-01 00:00:00
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
更新日期:2012-03-01 00:00:00
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
更新日期:2005-07-01 00:00:00
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
更新日期:2010-01-01 00:00:00
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
更新日期:1982-09-01 00:00:00
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
更新日期:2004-04-01 00:00:00
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:
更新日期:1995-06-01 00:00:00
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
更新日期:1997-08-01 00:00:00
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
更新日期:2004-02-01 00:00:00
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
更新日期:2002-01-01 00:00:00
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
更新日期:1976-05-01 00:00:00
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
更新日期:2001-02-01 00:00:00
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
更新日期:2007-09-01 00:00:00
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
更新日期:2012-11-01 00:00:00
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
更新日期:2008-09-01 00:00:00
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
更新日期:2012-07-15 00:00:00
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
更新日期:2011-05-01 00:00:00
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
更新日期:2010-02-01 00:00:00
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
更新日期:2020-03-01 00:00:00
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
更新日期:1988-07-01 00:00:00
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
更新日期:2009-12-01 00:00:00
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
更新日期:2002-11-01 00:00:00
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
更新日期:2015-09-01 00:00:00
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
更新日期:2015-02-01 00:00:00
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
更新日期:2020-07-01 00:00:00
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
更新日期:1995-12-01 00:00:00
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
更新日期:1993-04-01 00:00:00