Abstract:
AIMS:Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood. METHODS AND RESULTS:We have identified novel mutations in the desmosomal cadherin desmocollin 2 (DSC2 R203C, L229X, T275M, and G371fsX378). The two missense mutations (DSC2 R203C and T275M) have been functionally characterized, together with a previously reported frameshift variant (DSC2 A897fsX900), to examine their pathogenic potential towards PG's functions at the ID. The three mutant proteins were transiently expressed in various cellular systems and assayed for expression, processing, localization, and binding to other desmosomal components in comparison to wild-type DSC2a protein. The two missense mutations showed defects in proteolytic cleavage, a process which is required for the functional activation of mature cadherins. In both cases, this is thought to cause a reduction of functional DSC2 at the desmosomes in cardiac cells. In contrast, the frameshift variant was incorporated into cardiac desmosomes; however, it showed reduced binding to PG. CONCLUSION:Despite different modes of action, for all three variants, the reduced ability to provide a ligand for PG at the desmosomes was observed. This is in agreement with the reduced intensity of PG at these structures observed in ARVC patients.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Gehmlich K,Syrris P,Peskett E,Evans A,Ehler E,Asimaki A,Anastasakis A,Tsatsopoulou A,Vouliotis AI,Stefanadis C,Saffitz JE,Protonotarios N,McKenna WJdoi
10.1093/cvr/cvq353subject
Has Abstractpub_date
2011-04-01 00:00:00pages
77-87issue
1eissn
0008-6363issn
1755-3245pii
cvq353journal_volume
90pub_type
杂志文章abstract:BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00320-5
更新日期:2001-04-01 00:00:00
abstract:AIMS:It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated. METHODS AND RESULTS:Immunohi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp385
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:Earlier studies have revealed sarcolemmal (SL) defects in congestive heart failure due to myocardial infarction; however, the mechanisms of SL changes in the failing heart are poorly understood. Since congestive heart failure is associated with various metabolic abnormalities including a deficiency of carniti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00089-9
更新日期:1999-06-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.10.875
更新日期:1991-10-01 00:00:00
abstract::The role of mediators of inflammation in the pathogenesis and evolution of myocardial infarction has attracted increased interest as interventions which inhibit the inflammatory response after coronary artery occlusion have been shown to decrease infarct size. The distribution of fibrinogen and albumin in ischaemia my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.1.36
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.001
更新日期:2007-11-01 00:00:00
abstract::The cardiospecificity of the MB isoenzyme of creatine kinase, EC 2.7.3.2, (CK) with its associated diagnostic and research value has resulted in the development of a number of procedures for the separation and quantitation of the three isoenzymes of CK. In our experience methods involving cellulose acetate electrophor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.94
更新日期:1977-03-01 00:00:00
abstract:OBJECTIVE:Adenosine inhibits neutrophil adhesion and injury to isolated cardiac myocytes. In the present study, the contribution of selectin and CD18 interactions to neutrophil-myocyte adhesion and their sensitivity to adenosine were assessed. METHODS:Activated human neutrophils and canine myocytes were incubated with...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00052-1
更新日期:1996-08-01 00:00:00
abstract:OBJECTIVE:We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS:Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the follo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00455-8
更新日期:2002-08-15 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:AIMS:Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with aging in HFrEF potentially leading to targeted therapies in this vulnerable...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa279
更新日期:2020-10-01 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
abstract:OBJECTIVE:To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS:Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril suppl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00239-4
更新日期:1999-12-01 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
更新日期:2000-05-01 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
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:Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00068-6
更新日期:1998-09-01 00:00:00
abstract:AIMS:The metabolic syndrome (MS) leads to myocardial fibrosis (MF) and diastolic dysfunction. Statins have proven beneficial effects in MS, but their impact on cardiac remodelling is uncertain. We examined the effects and mechanisms of chronic statin treatment on cardiac remodelling, e.g. fibrosis and diastolic propert...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt070
更新日期:2013-07-01 00:00:00
abstract::Experimental studies have provided evidence that the autonomic nervous activity is modulated by oestrogen. Such modulation at central and peripheral levels tends to suppress sympathetic but elevate parasympathetic tone to the cardiovascular system. Thus, available data support the view that cardiovascular protection b...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:
更新日期:1995-08-01 00:00:00
abstract:OBJECTIVE:Progressive loss of cardiomyocytes is one of the most important pathogenic characteristics of heart failure. Apoptosis may be an important mode of cell death in heart failure but it must be demonstrated by multiple criteria and not just TUNEL staining alone. Previously, we and others have demonstrated that be...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00290-5
更新日期:2001-08-01 00:00:00
abstract::The contractile response to beta-adrenoceptor stimulation has been found to be reduced in single myocytes from failing human ventricle. A portion of that reduction was statistically related to the age of the patient. We have developed a method for obtaining viable contracting myocytes from small biopsies of human vent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Mayer waves are oscillations of arterial pressure occurring spontaneously in conscious subjects at a frequency lower than respiration (approximately 0.1 Hz in humans). Mayer waves are tightly coupled with synchronous oscillations of efferent sympathetic nervous activity and are almost invariably enhanced during states...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.11.008
更新日期:2006-04-01 00:00:00
abstract::Felodipine (4(2,3-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonyl pyridine)), a selective vasodilating anti-hypertensive drug, was used in the treatment of spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto rats (WKYs) from age 6 to 14 weeks, ie during the time of high blo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.528
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVES:Collagen synthesis is one of the major mechanisms of primary atherosclerotic plaque growth and is likely to be similarly important in restenosis. The patterns of collagen gene expression in human restenosis and associations with thrombosis/hemorrhage have not been described. METHODS:Using human coronary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract:AIMS:Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:Mice ...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt235
更新日期:2014-01-01 00:00:00
abstract:AIMS:Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn140
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVE:Decay kinetics of the voltage-gated L-type Ca(2+) current (I(CaL)) control the magnitude of Ca(2+) influx during the cardiac action potential. We investigated the influence of changes in diastolic membrane potential on I(CaL) decay kinetics in cardiac cells. METHODS:Cells were isolated enzymatically from rat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00107-3
更新日期:2000-08-01 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:OBJECTIVE:Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the alpha1A-adrenergic receptors (alpha1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI). METHODS:We subjected alpha1A...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.06.015
更新日期:2006-09-01 00:00:00
abstract::The effect of acetylcholine on the aconitine induced delayed afterdepolarisation and triggered electrical activities under nominally calcium free conditions were studied in frog atrium and ventricle. The changes in intracellular potassium activity were also examined. The aconitine induced delayed afterdepolarisation a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.11.804
更新日期:1987-11-01 00:00:00