Abstract:
AIMS:Vascular remodelling and aortic aneurysm formation are induced mainly by inflammatory responses in the adventitia and media. However, relatively little is known about the mechanistic significance of endothelium in the pathogenesis of these vascular disorders. The transcription factor nuclear factor-kappa B (NF-κB) regulates the expressions of numerous genes, including those related to pro-inflammatory responses. Therefore, to investigate the roles of endothelial pro-inflammatory responses, we examined the impact of blocking endothelial NF-κB signalling on intimal hyperplasia and aneurysm formation. METHODS AND RESULTS:To block endothelial NF-κB signalling, we used transgenic mice expressing dominant-negative IκBα selectively in endothelial cells (E-DNIκB mice). E-DNIκB mice were protected from the development of cuff injury-induced neointimal formation, in association with suppressed arterial expressions of cellular adhesion molecules, a macrophage marker, and inflammatory factors. In addition, the blockade of endothelial NF-κB signalling prevented abdominal aortic aneurysm formation in an experimental model, hypercholesterolaemic apolipoprotein E-deficient mice with angiotensin II infusion. In this aneurysm model as well, aortic expressions of an adhesion molecule, a macrophage marker, and inflammatory factors were suppressed with the inhibited expression and activity of matrix metalloproteinases in the aorta. CONCLUSION:Endothelial NF-κB activation up-regulates adhesion molecule expression, which may trigger macrophage infiltration and inflammation in the adventitia and media. Thus, the endothelium plays important roles in vascular remodelling and aneurysm formation through its intracellular NF-κB signalling.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Saito T,Hasegawa Y,Ishigaki Y,Yamada T,Gao J,Imai J,Uno K,Kaneko K,Ogihara T,Shimosawa T,Asano T,Fujita T,Oka Y,Katagiri Hdoi
10.1093/cvr/cvs298subject
Has Abstractpub_date
2013-01-01 00:00:00pages
106-14issue
1eissn
0008-6363issn
1755-3245pii
cvs298journal_volume
97pub_type
杂志文章abstract:OBJECTIVE:Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. METHODS:Rat aortic endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00269-2
更新日期:2000-01-14 00:00:00
abstract:AIMS:Vascular calcification often occurs with advancing age, atherosclerosis, and metabolic disorders such as diabetes mellitus and end-stage renal disease. Vascular calcification is associated with cardiovascular events and increased mortality. Nitric oxide (NO) is crucial for maintaining vascular function, but little...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm049
更新日期:2008-01-01 00:00:00
abstract:AIMS:Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy217
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVE:Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.09.015
更新日期:2006-01-01 00:00:00
abstract:AIMS:The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw233
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVES:We performed the following study to define the effects of acute cardiac lymphatic obstruction on left ventricular (LV) systolic and diastolic function. METHODS:Cardiac lymphatic obstruction was created in 8 pentobarbital-anesthetized dogs by identifying (Evans blue) and ligating the right and left epicardia...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00177-0
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist. METHODS:ApoE-deficient and C57BL/6J control mice...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00469-2
更新日期:2002-02-01 00:00:00
abstract::Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechani...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00367-4
更新日期:2001-10-01 00:00:00
abstract::Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Most previous investigations focused on the role of homocysteine as direct pathogenetic factor for these adverse vascular events. However, the exact pathophysiological mechanism is still unknown. In this review we discuss the hypothesis tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(03)00462-0
更新日期:2003-08-01 00:00:00
abstract:AIMS:Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz305
更新日期:2021-01-01 00:00:00
abstract::We studied the effects of intravenously administered autonomic agents, the calcium channel blocker diltiazem, and Class I and III anti-arrhythmic agents on a re-entry model for atrial tachycardia in seven conscious dogs. The model was created by a Y-shaped incision in the intercaval region and front free wall of the r...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.5.400
更新日期:1989-05-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine if prostaglandin like activity might be involved in changes due to exercise training in the coronary flow responses to hypoxia. DESIGN:The coronary flow response to hypoxia was measured under constant perfusion pressure in isolated perfused hearts from 12 endurance exercise tra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.733
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVES:Anthracyclines cause apoptotic death in many cell types through activation of the ceramide pathway. We tested the hypothesis that doxorubicin induces cardiac myocyte apoptosis through ceramide generation. METHODS:Adult rat ventricular myocytes were grown in the presence of 10% fetal calf serum, and exposed ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00142-x
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVE:Important physiological and pathophysiological conditions are associated with changes in secretion and synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The aim of this study was to examine the effects of mechanical stretch and endothelin-1 on ANF and BNP secretion and gene exp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.10.1519
更新日期:1994-10-01 00:00:00
abstract::Inorganic nitrate from dietary and endogenous sources is emerging as a substrate for in vivo generation of nitric oxide (NO) and other reactive nitrogen oxides. Dietary amounts of nitrate clearly have robust NO-like effects in humans, including blood pressure reduction, inhibition of platelet aggregation, and vasoprot...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq325
更新日期:2011-02-15 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
abstract::The effects of increasing oxygen tension from fetal to neonatal levels and of incubation in the cyclo-oxygenase inhibitor, indomethacin, on the response of isolated rings of neonatal rabbit ductus arteriosus and aorta to noradrenaline were studied in vitro. Increasing oxygen tension did not affect the sensitivity, as ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.12.910
更新日期:1988-12-01 00:00:00
abstract:AIMS:The regulation of vascular diameter by vasoconstrictors and vasodilators requires that vascular smooth muscle cells (VSMCs) be physically coupled to extracellular matrix (ECM) and neighbouring cells in order for a vessel to mechanically function and transfer force. The hypothesis was tested that integrin-mediated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs239
更新日期:2012-10-01 00:00:00
abstract::Changes in left ventricular internal diameter resulting from increasing intrapericardial pressure induced by increasing the pericardial fluid volume were studied in closed chest, anaesthetized dogs. Left ventricular internal diameters were measured by placing an ultrasonic dimension catheter in the left ventricle at t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.6.707
更新日期:1975-11-01 00:00:00
abstract::The effect of axial rotation on flow through and pressure gradient across saphenous vein segments was studied using 15 cadaver long saphenous veins. A significant reduction in flow occurred at a mean rotation of 25 degrees/cm and a significant increase in head loss across the segments occurred at a mean rotation of 23...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.4.538
更新日期:1975-07-01 00:00:00
abstract:AIMS:This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta. METHODS AND RESULTS:Aortic segments from orchidectomized and control male Sprague-Dawley ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm059
更新日期:2008-02-01 00:00:00
abstract::The isolated perfused heart has been used increasingly during the last decade as a model for identifying actions of drugs on ventricular fibrillation (VF) induced by myocardial ischaemia. In addition, it has been used to explore the mechanisms responsible for the initiation and maintenance of VF, the concept of endoge...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(98)00083-2
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND:The mechanism of defibrillation is controversial. Reentry appearing immediately after the shock has been shown to be responsible for defibrillation failure in some studies while other studies have demonstrated that a rapid train of focal activations with the first focus appearing >50 ms after the shock is re...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.10.009
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:Inducible costimulator (ICOS) is a member of the CD28 family. Although inflammation is an essential pathological feature of myocarditis, the role of ICOS in myocarditis remains unclear. METHODS AND RESULTS:Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00334-1
更新日期:2003-07-01 00:00:00
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
更新日期:2005-07-01 00:00:00
abstract:AIMS:G-protein-coupled receptors (GPCRs) modulate vascular tone, at least in part, via matrix metalloproteinase (MMP) transactivation of the epidermal growth factor receptor (EGFR). We previously have identified novel signalling pathways downstream of the EGFR suggestive of mitogen-activated protein kinase and mitochon...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp230
更新日期:2009-12-01 00:00:00
abstract:AIMS:Heparanase, which specifically cleaves carbohydrate chains of heparan sulfate, has been implicated in the pathology of diabetes-associated complications. Using high glucose (HG) to replicate hyperglycaemia observed following diabetes, the present study was designed to determine the mechanism by which HG initiates ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq051
更新日期:2010-07-01 00:00:00
abstract:AIMS:The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined. METHODS AND RESULTS:Whole-cell patch-clamp recordings showed outward-rectifying currents in hum...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp153
更新日期:2009-08-01 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:STUDY OBJECTIVE:The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN:Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); ter...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.754
更新日期:1990-09-01 00:00:00