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 hypothesized that m-calpain participates in the shear pattern-dependent EC barrier maintenance through RhoA signalling. METHODS AND RESULTS:m-Calpain expression levels in the intima in the inferior aspect of mouse aortic arch where DF dominates were higher than those in adjacent regions. Elevation in transendothelial albumin permeability, which was induced by administration of a calpain inhibitor (ALLM), was prominent in the inferior arch; moreover, this elevation was abolished by Rho kinase (ROCK) inhibitor (Y-27632). Similarly, short interfering RNA (siRNA)-induced silencing of m-calpain resulted in increased RhoA activity and hyperpermeability in the aortic arch, which was accompanied by ROCK inhibitor-sensitive phosphorylation of downstream effecter LIM kinase 2 (LIMK2), stress fibre accumulation in endothelium and enhanced interendothelial gaps. Exposure of human umbilical vein endothelial cells to LF diminished RhoA activity; in contrast, DF facilitated the activity. siRNA-induced m-calpain silencing further accelerated the DF-induced RhoA overactivation, phosphorylation of LIMK2, and cytoskeletal rearrangement, resulting in barrier dysfunction in the cells. CONCLUSION:Our findings revealed relatively high m-calpain expression levels in the inferior arch. The m-calpain activity antagonizes DF-induced overactivation of RhoA/ROCK/LIMK2 signalling and subsequent cytoskeletal rearrangement in ECs, which leads to barrier improvement.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Miyazaki T,Honda K,Ohata Hdoi
10.1093/cvr/cvp311subject
Has Abstractpub_date
2010-02-01 00:00:00pages
530-41issue
3eissn
0008-6363issn
1755-3245pii
cvp311journal_volume
85pub_type
杂志文章abstract:AIMS:Insulin (Ins) resistance (IRES) associates to increased cardiovascular risk as observed in metabolic syndrome. Chronic stimulation of beta-adrenergic receptors (betaAR) due to exaggerated sympathetic nervous system activity is involved in the pathogenesis of IRES. The cellular levels of G protein coupled receptor ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp252
更新日期:2009-12-01 00:00:00
abstract:AIM:The interaction between TNF-like weak inducer of apoptosis (TWEAK, Tnfsf12) and the receptor, fibroblast growth factor-inducible 14 (Fn14), regulates vascular damage through different mechanisms, including inflammation. Oxidative stress plays a major role in inflammation and the development of atherosclerosis, but ...
journal_title:Cardiovascular research
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doi:10.1093/cvr/cvv204
更新日期:2015-10-01 00:00:00
abstract::The effect on the microcirculation of long term administration of the alpha 1 blocker prazosin, which increases peripheral blood flow, was studied in skeletal muscles with differing metabolic profiles. Prazosin (50 mg.litre-1), given ad libitum for 5 weeks in the drinking water, resulted in an increase in capillarity ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.11.913
更新日期:1989-11-01 00:00:00
abstract:OBJECTIVE:Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS:To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00278-4
更新日期:2001-07-01 00:00:00
abstract:OBJECTIVE:The aim was to test the hypothesis that in normal humans angiotensin II would stimulate local release of noradrenaline under basal conditions or during a sympathetic stimulus provided by lower body negative pressure (LBNP). METHODS:Nine healthy volunteers received intra-arterial infusions of angiotensin II, ...
journal_title:Cardiovascular research
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doi:10.1093/cvr/28.5.663
更新日期:1994-05-01 00:00:00
abstract::Blood vessels are permanently exposed to stretch and shear stress due to blood pressure and blood flow. Significant variations in the mechanical environment, of physiological or pathophysiological nature, occur in vivo. These trigger acute changes in vessel diameter that tend to restore basal levels of tensile and she...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.05.008
更新日期:2006-07-15 00:00:00
abstract::Platelet-dependent thrombus formation is a key event in the pathogenesis of acute myocardial infarction (AMI). Platelets mediate both thrombotic occlusion of the entire epicardial coronary artery and also accumulate in the microcirculation resulting in impairment of microcirculation and provoking myocardial ischemia d...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2003.11.036
更新日期:2004-02-15 00:00:00
abstract:AIMS:To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS:Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa241
更新日期:2020-08-10 00:00:00
abstract:OBJECTIVE:The aim was to test for the presence of cAMPi activated and ATPo activated chloride conductances (ICl(cAMP) and ICl(ATP)) in mouse ventricular myocytes. METHODS:Membrane currents were measured in enzymatically dissociated ventricular myocytes using the whole cell configuration of the patch clamp technique. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract:OBJECTIVE:Vascular endothelial growth factor (VEGF), secreted by vascular cells and a variety of tumour cells, is a potent angiogenic factor. Since nitric oxide (NO) seems to play a key role in the VEGF-induced proliferation of endothelial cells, the aim of the present study was to determine whether VEGF stimulates end...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00228-4
更新日期:1999-03-01 00:00:00
abstract:AIMS:Cardiac β-adrenergic receptors (β-AR) are key regulators of cardiac haemodynamics and size. The scaffolding protein A-kinase anchoring protein 79/150 (AKAP5) is a key regulator of myocardial signalling by β-ARs. We examined the function of AKAP5 in regulating cardiac haemodynamics and size, and the role of β-ARs a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu209
更新日期:2014-11-01 00:00:00
abstract::The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.570
更新日期:1985-09-01 00:00:00
abstract:AIM:Diabetes is a conventional risk factor for atherosclerotic cardiovascular disease and myocardial infarction (MI) is the most common cause of death among these patients. Mesenchymal stromal cells (MSCs) in patients with type 2 diabetes (T2DM) and atherosclerosis have impaired ability to suppress activated T-cells (i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa118
更新日期:2020-04-27 00:00:00
abstract::Protein and lipid oxidation-mainly by mitochondrial reactive oxygen species (mtROS)-was proposed as a crucial determinant of health and lifespan. Angiotensin II (Ang II) enhances ROS production by activating NAD(P)H oxidase and uncoupling endothelial nitric oxide synthase (NOS). Ang II also stimulates mtROS production...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq285
更新日期:2011-01-01 00:00:00
abstract:AIMS:Cardiovascular research requires complex and functionally intact experimental models. Due to major differences in the cellular and subcellular composition of the myocardium between species, the use of human heart tissue is highly desirable. To enhance the experimental use of the human myocardium, we established me...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr259
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVES:Injury stimulates smooth muscle cell (SMC) migration and proliferation by mechanisms that are incompletely understood. Surgical preparative injury is an important determinant of neointimal thickening in human saphenous vein bypass grafts. We investigate here whether basement-membrane-degrading metalloprotein...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00211-8
更新日期:1997-02-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to determine whether the deleterious effects of anaesthesia on cardiac muscle function were due to disturbance of protein synthesis. Comparative investigations were made on anaerobic and aerobic skeletal muscles, and plasma insulin and growth hormone levels were also measured to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.4.314
更新日期:1991-04-01 00:00:00
abstract:OBJECTIVE:Mechanoelectric Feedback, a mechanical intervention inducing an electrical change, is gaining credence as a cause of cardiac arrhythmia in the clinical situation. However, the precise mechanism is unknown. To elucidate this we investigated mechanical and chemical modulation of stretch-induced premature ventri...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00314-3
更新日期:1998-04-01 00:00:00
abstract:AIMS:Vascular inflammation is a major atherogenic factor and Toll-like receptor (TLR) 2 ligands, including bacterial and serum lipoproteins, seem to be involved in atherogenesis. On this basis, we analysed the effect of lipoproteins and different lipid components on TLR2-dependent signalling. METHODS AND RESULTS:In TL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
abstract::STUDY OBJECTIVE - The aim of the study was to determine the changes in the beta adrenergic system induced by cardiac hypertrophy due to valvular aortic stenosis. DESIGN - Density of beta adrenoceptors, cardiac tissue noradrenalime concentrations, coronary blood flow (using radioactive microspheres), and haemodynamic v...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.1.65
更新日期:1990-01-01 00:00:00
abstract::Oxygen-derived free radicals are thought to contribute to the initiation and progression of cardiovascular disease via several different mechanisms, such as consumption of nitric oxide, oxidation of proteins and lipids, and activation of redox-sensitive signalling cascades. Vascular NADPH oxidases are important source...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.08.007
更新日期:2005-01-01 00:00:00
abstract:AIMS:We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients. METHODS AND RESULTS:ApoE(-/-)RAG2(-/-) mice received four intravenous injections of sa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm034
更新日期:2008-02-01 00:00:00
abstract::End-diastolic current thresholds have been measured in 12 open-chested dogs with epicardial disc electrodes ranging in radius from 0.01 to 9.0 mm. The current threshold for cathodal 1 ms impulses proved to be independent of electrode size for radii smaller than 0.2 mm and proportional to the radius to the power 1.5 fo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.8.477
更新日期:1978-08-01 00:00:00
abstract::Acute coronary syndromes result from fissure, erosion or rupture of a vulnerable atherosclerotic plaque. The characteristics of a vulnerable plaque include a large lipid pool, an abundance of inflammatory cells and mediators, a reduced smooth muscle cell and collagen content and a thin overlying fibrous cap. Potential...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(98)00279-x
更新日期:1999-02-01 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:AIMS:Human congenital heart disease linked to mutations in the homeobox transcription factor, NKX2-5, is characterized by cardiac anomalies, including atrial and ventricular septal defects as well as conduction and occasional defects in contractility. In the mouse, homozygous germline deletion of Nkx2-5 gene results in...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr037
更新日期:2011-07-15 00:00:00
abstract:OBJECTIVE:The aim was to test the hypothesis that nitric oxide (or a related compound) contributes to the coronary vasodilatation during physiological increases of myocardial O2 consumption that occur with exercise. METHODS:Active hyperaemia associated with graded treadmill exercise and coronary reactive hyperaemia we...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.1.119
更新日期:1994-01-01 00:00:00
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...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt126
更新日期:2013-08-01 00:00:00
abstract::The second messenger cyclic guanosine 3'5' monophosphate (cGMP) and its downstream effector protein kinase G (PKG) have been discovered more than 40 years ago. In vessels, PKG1 induces smooth muscle relaxation in response to nitric oxide signalling and thus lowers systemic and pulmonary blood pressure. In platelets, P...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw107
更新日期:2016-07-15 00:00:00
abstract:OBJECTIVE:The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS:Experiments were done on fragments of papillary muscles from the right ventricles of gu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.371
更新日期:1992-04-01 00:00:00