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 reduced in obesity and associated with leptin resistance. In this study, we examined the role of apoE in mediating the effects of leptin on vascular lesion formation. METHODS AND RESULTS:Leptin was administered to apoE knockout (apoE-/-) mice via osmotic pumps to increase its circulating levels. Morphometric analysis revealed that leptin did not alter neointima formation and failed to increase α-actin- or PCNA-immunopositive SMCs after vascular injury. Similar findings were obtained after analysis of atherosclerotic lesions. Comparison of apoE-/-, wild-type, or LDL receptor-/- mice and functional analyses in aortic SMCs from WT or apoE-/- mice or human arterial SMCs after treatment with small interfering (si)RNA or heparinase revealed that leptin requires the presence of apoE, expressed, secreted and bound to the cell surface, to fully activate leptin receptor signalling and to promote SMC proliferation and neointima formation. Mechanistically, leptin induced the phosphorylation and membrane translocation of caveolin (cav)-1, and apoE down-regulation or caveolae disruption inhibited the leptin-induced p47phox activation, ROS formation and SMC proliferation. Finally, leptin failed to increase neointima formation in mice lacking cav-1. CONCLUSION:Our findings suggest that apoE mediates the effects of leptin on vascular lesion formation by stabilizing cav-1-enriched cell membrane microdomains in SMCs, thus allowing NADPH oxidase assembly and ROS-mediated mitogenic signalling.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Schroeter MR,Leifheit-Nestler M,Hubert A,Schumann B,Glückermann R,Eschholz N,Krüger N,Lutz S,Hasenfuss G,Konstantinides S,Schäfer Kdoi
10.1093/cvr/cvt126subject
Has Abstractpub_date
2013-08-01 00:00:00pages
555-65issue
3eissn
0008-6363issn
1755-3245pii
cvt126journal_volume
99pub_type
杂志文章abstract:OBJECTIVE:Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00136-9
更新日期:1998-11-01 00:00:00
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
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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:The aim was to estimate the relative contributions of the various intracellular and sarcolemmal systems to the relaxation of the systolic calcium transient. METHODS:The experiments were performed on isolated rat ventricular myocytes. The cells were loaded with the fluorescent indicator indo-1 in order to mea...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1826
更新日期:1993-10-01 00:00:00
abstract:AIMS:Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that contributes to pathogenic cardiac remodelling via mechanisms that involve oxidative stress. However, the direct impact of TGF-beta1 on contractile function of ventricular myocytes is incompletely understood. METHODS AND RESULTS:Reacti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm022
更新日期:2008-01-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to test an intermittent ECG synchronised suction device which was added to a coronary vein retroinfusion system (selective suction and retroinfusion = SSR) in order to transport oxygenated fluid more efficiently into ischaemic myocardium. DESIGN:The suction period preceding the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.6.456
更新日期:1990-06-01 00:00:00
abstract::Intracellular acidosis exerts substantial effects on the contractile performance of the heart. Soon after the onset of acidosis, contractility diminishes, largely due to a decrease in myofilament Ca(2+) responsiveness. This decrease in contractility is followed by a progressive recovery that occurs despite the persist...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.12.002
更新日期:2007-03-01 00:00:00
abstract::The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasingly apparent is tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn054
更新日期:2008-07-15 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
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.10.1586
更新日期:1994-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt238
更新日期:2014-01-01 00:00:00
abstract::An in situ preparation of the rabbit thoracic aorta has been used to study the transport of short-lived radioactive isotopes of oxygen (15O16O), nitrogen (13N14N) and an isotope of xenon (133Xe) from 0.9% NaCl into the artery wall. At a luminal hydrostatic pressure of 2 kPa the uptake of all three isotopes by the inti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.8.456
更新日期:1981-08-01 00:00:00
abstract::Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy006
更新日期:2018-03-15 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs211
更新日期:2012-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00167-8
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE AND METHODS:In this study, we investigated whether Ca(2+) transients are altered in Purkinje cell aggregates dispersed from the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00725-3
更新日期:2003-03-01 00:00:00
abstract:AIMS:A problem in generating artificial tissues is supplying nutrients to cells within 3D constructs. The use of a decellularized biological vascularized matrix with preserved pedicles (BioVaM), as a scaffold, appears to aid the generation of perfusable tissue constructs in vitro. To prevent vessel occlusion upon impla...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp370
更新日期:2010-03-01 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::Controversy exists as to whether the diabetic heart is more or less sensitive to ischemic injury. Although a considerable number of experimental studies have directly determined the effects of ischemia on the diabetic heart, there is still no general agreement as to whether metabolic changes within the myocardium cont...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00037-0
更新日期:1997-04-01 00:00:00
abstract::Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentiall...
journal_title:Cardiovascular research
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更新日期:2013-03-01 00:00:00
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journal_title:Cardiovascular research
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更新日期:2004-02-15 00:00:00
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更新日期:2000-12-01 00:00:00
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doi:10.1016/s0008-6363(98)00180-1
更新日期:1998-11-01 00:00:00
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更新日期:1977-05-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.167
更新日期:1977-03-01 00:00:00
abstract::The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular ef...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.07.006
更新日期:2004-11-01 00:00:00
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journal_title:Cardiovascular research
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doi:10.1016/j.cardiores.2003.10.013
更新日期:2004-02-15 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.11.020
更新日期:2006-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(96)00134-4
更新日期:1996-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.1.42
更新日期:1986-01-01 00:00:00