Abstract:
AIMS:TRPM2 is a Ca(2+)-permeable cationic channel of the transient receptor potential (TRP) superfamily that is linked to apoptotic signalling. Its involvement in cardiac pathophysiology is unknown. The aim of this study was to determine whether the pro-apoptotic cytokine tumour necrosis factor-α (TNF-α) induces a TRPM2-like current in murine ventricular cardiomyocytes. METHODS AND RESULTS:Adult isolated cardiomyocytes from C57BL/6 mice were exposed to TNF-α (10 ng/mL). Western blotting showed TRPM2 expression, which was not changed after TNF-α incubation. Using patch clamp in whole-cell configuration, a non-specific cation current was recorded after exposure to TNF-α (ITNF), which reached maximal steady-state amplitude after 3 h incubation. ITNF was inhibited by the caspase-8 inhibitor z-IETD-fmk, the antioxidant N-acetylcysteine, and the TRPM2 inhibitors clotrimazole, N-(P-amylcinnamoyl) anthranilic acid and flufenamic acid (FFA). TRPM2 has previously been shown to be activated by ADP-ribose, which is produced by poly(ADP-ribose) polymerase 1 (PARP-1). TNF-α exposure resulted in increased poly-ADP-ribosylation of proteins and the PARP-1 inhibitor 3-aminobenzamide inhibited ITNF. TNF-α exposure increased the mitochondrial production of reactive oxygen species (ROS; measured with the fluorescent indicator MitoSOX Red), and this increase was blocked by the caspase-8 inhibitor z-IETD-fmk. Clotrimazole and TRPM2 inhibitory antibody decreased TNF-α-induced cardiomyocyte death. CONCLUSION:These results demonstrate that TNF-α induces a TRPM2 current in adult ventricular cardiomyocytes. TNF-α induces caspase-8 activation leading to ROS production, PARP-1 activation, and ADP-ribose production. TNF-induced TRPM2 activation may contribute to cardiomyocyte cell death.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Roberge S,Roussel J,Andersson DC,Meli AC,Vidal B,Blandel F,Lanner JT,Le Guennec JY,Katz A,Westerblad H,Lacampagne A,Fauconnier Jdoi
10.1093/cvr/cvu112subject
Has Abstractpub_date
2014-07-01 00:00:00pages
90-9issue
1eissn
0008-6363issn
1755-3245pii
cvu112journal_volume
103pub_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:P2X receptors (P2XRs) mediate sympathetic control and autoregulation of renal circulation triggering preglomerular vasoconstriction, which protects glomeruli from elevated pressures. Although previous studies established a casual link between glomerular susceptibility to hypertensive injury and decreased preglomer...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu249
更新日期:2015-02-01 00:00:00
abstract::The potent anaphylatoxin C3a was measured in the peripheral blood of eleven patients receiving radiocontrast agents whilst undergoing coronary angiography. In seven patients C3a levels were raised during this procedure and in three of these the anaphylatoxin was increased between four and tenfold. In four patients C3a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.85
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVES:M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS:We simulated action potent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.02.016
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:The endothelium is a newly recognised target tissue of parathyroid hormone (PTH). It is not clear whether hyperparathyroidism affects endothelial function and whether parathyroidectomy (Ptx) has an influence on arterial vessel wall properties. We studied brachial flow-mediated vasodilation (FMD) and brachial ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00130-9
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:We investigated the influence of experimental hyperlipidemia on the formation of cardiac NO, superoxide, and peroxynitrite (ONOO(-)) in rat hearts. METHODS:Wistar rats were fed 2% cholesterol-enriched diet or normal diet for 8 weeks. Separate groups of normal and hyperlipidemic rats were injected twice intra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00330-4
更新日期:2003-06-01 00:00:00
abstract::We studied the effects of intracoronary vasopressin on the relationship between pressure and flow in the coronary circulation of anaesthetised swine. In addition to measurements at control levels, diastolic pressure-flow relationships were constructed from steady-state points below a coronary pressure of 50 mmHg, wher...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.7.433
更新日期:1985-07-01 00:00:00
abstract:AIMS:Placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an ant...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp380
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:The aim was to determine the ionic basis of action potential lengthening associated with cardiac hypertrophy. METHODS:Action potentials and ionic currents of left ventricular myocytes isolated from normal and hypertrophied hearts were recorded with patch pipettes. Since cardiac hypertrophy is a time dependen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.8.1180
更新日期:1994-08-01 00:00:00
abstract:BACKGROUND:The atrial natriuretic peptide (ANP) family is a complex system consisting of at least three polypeptides and at least three types of receptor. Each peptide interacts with different types of receptor at varying degrees of affinity. To determine if natriuretic peptide levels influence natriuretic peptide rece...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00038-9
更新日期:2000-06-01 00:00:00
abstract:AIMS:Adrenomedullin (AM) is a multifunctional peptide hormone that plays a significant role in vasodilation and angiogenesis. Lymphoedema is a common but refractory disorder that is difficult to be treated with conventional therapy. We therefore investigated whether AM promotes lymphangiogenesis and improves lymphoedem...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn228
更新日期:2008-12-01 00:00:00
abstract:Aims:The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arteria...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx015
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVES:Nitric oxide (NO) has complex effects on myocardial function particularly following ischaemia-reperfusion. The goal of this study was to examine the result of repetitive myocardial stunning on myocardial NO release and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. METHODS AND RESULTS:...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00149-2
更新日期:1999-08-15 00:00:00
abstract:UNLABELLED:Recent investigations have established the feasibility of using exogenously delivered angiogenic growth factors to increase collateral artery development in animal models of myocardial and hindlimb ischemia. OBJECTIVE:Our aim was to evaluate the ability of a stabilized form of acidic fibroblast growth facto...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00522-4
更新日期:2003-10-01 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::Electrophysiologic remodeling is a process whereby heart disease alters the electrophysiologic properties of cardiac tissue. These alterations, in turn, can cause or exacerbate disease-related arrhythmias. Ion channels are the fundamental molecular units underlying cardiac electrophysiology, and it therefore follows t...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00063-2
更新日期:1999-05-01 00:00:00
abstract::Hyponatremia is a frequent electrolyte disorder. It is often found in congestive cardiac failure, liver cirrhosis, plasma volume contraction and in SiADH. In these disorders hyponatremia is caused by nonosmotic vasopressin and sustained fluid intake. This provides a rationale for V2 vasopressin receptor antagonists in...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00288-7
更新日期:2001-08-15 00:00:00
abstract::The cardioprotective effects of mioflazine, a recently developed cardiovascular drug, were investigated in 41 anaesthetised open chest Beagle dogs subjected to 1 h normothermic global myocardial ischaemia. The severity of the model is evidenced by the finding that only one out of 20 control dogs could be weaned from e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.9.528
更新日期:1984-09-01 00:00:00
abstract:OBJECTIVES:Coronary microvascular endothelial cells (CMVEs) can modulate the contractile performance of the adjacent myocardium by the release of agents such as nitric oxide (NO). Most previous studies using CMVEs have been done in situ, in the intact organ. We set out to study possible differences in NO synthase (NOS)...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00336-8
更新日期:1999-06-01 00:00:00
abstract:OBJECTIVE:Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affect myocardial oxygen consumption. Although NOS3 is a constitutive protein, its levels of expression can be modi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00059-5
更新日期:1998-06-01 00:00:00
abstract:AIMS:The human ether-a-go-go-related gene (hERG) encodes the rapidly activating delayed rectifier potassium channel (IKr). Malfunction of hERG/IKr is the primary cause of acquired long QT syndrome (LQTS), an electrical disorder of the heart that can cause arrhythmias and sudden death. Patients with autoimmune diseases ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy310
更新日期:2019-08-01 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:AIMS:Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signallin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv139
更新日期:2015-09-01 00:00:00
abstract::There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.740
更新日期:1986-10-01 00:00:00
abstract:AIMS:Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr158
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) on cardiac myocytes may be a critical step in cardiac inflammation associated with acute myocardial infarction and myocarditis. The aim of this study was to investigate the involvement of monocyte chemoattractant protein-1 (MCP-1), a homologue o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.8.1258
更新日期:1994-08-01 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:OBJECTIVE:Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.003
更新日期:2005-08-15 00:00:00
abstract:AIMS:Both cyclooxygenase-2 (COX-2) and the transcription factor signal transducer and activator of transcription 3 (Stat3) are involved in adaptive growth and survival of cardiomyocytes. In ventricular cardiomyocytes, prostaglandin E(2) (PGE(2)), a major COX-2 product, leads to adaptive growth via Stat3 activation, but...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn171
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:To explore long-term cardiac phenotype in transgenic (TG) mice with 300-fold overexpression of beta(2)-adrenergic receptors (AR). METHODS:Echocardiography was performed serially on a cohort of wild-type and TG mice (n=26 each) between 4 and 15 months of age. Survival was monitored and autopsy and histologica...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00187-5
更新日期:2000-12-01 00:00:00