Abstract：
AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to be involved in heart diseases. This study was to examine whether miR-195 regulates palmitate-induced cardiomyocyte apoptosis by targeting Sirt1, a known anti-apoptotic protein. METHODS AND RESULTS:In cultured neonatal mouse cardiomyocytes, palmitate up-regulated miR-195 expression, increased reactive oxygen species (ROS) production, and induced apoptosis as determined by up-regulation of caspase-3 activity and DNA fragmentation. Inhibition of miR-195 decreased ROS production and apoptosis in palmitate-stimulated cardiomyocytes. In contrast, a miR-195 mimic enhanced palmitate-induced ROS production and apoptosis. The induction of miR-195 correlated with a reduction in Sirt1 and Bcl-2. We further showed that miR-195 targeted and inhibited Sirt1 expression through two target sites located in the 3' un-translational region of Sirt1 mRNA. In concordance, inhibition of miR-195 increased Sirt1 protein in cardiomyocytes whereas the miR-195 mimic reduced it. Activation of Sirt1 or overexpression of Bcl-2 inhibited palmitate-induced apoptosis. On the other hand, inhibition of Sirt1 enhanced apoptosis. The inhibitory effect of Sirt1 on apoptosis was associated with a reduction in ROS. CONCLUSIONS:This study demonstrates a pro-apoptotic role of miR-195 in cardiomyocytes and identifies Sirt1 as a direct target of miR-195. The effect of miR-195 on apoptosis is mediated through down-regulation of Sirt1 and Bcl-2 and ROS production. Thus, miR-195 may be a new therapeutic target for lipotoxic cardiomyopathy.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Zhu H,Yang Y,Wang Y,Li J,Schiller PW,Peng Tdoi
10.1093/cvr/cvr145subject
Has Abstractpub_date
2011-10-01 00:00:00pages
75-84issue
1eissn
0008-6363issn
1755-3245pii
cvr145journal_volume
92pub_type
杂志文章abstract：:Having an apparently healthy, thriving infant fail to reach his/her first birthday is profoundly tragic. This tragedy is compounded when the infant's death is unexpected and unexplained, signed out as sudden infant death syndrome (SIDS). Despite impressive success and welcome reductions in these tragic deaths due in l...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2005.02.013
更新日期：2005-08-15 00:00:00
abstract：STUDY OBJECTIVE:The aim was to compare platelet function in diabetic and non-diabetic survivors of acute myocardial infarction and to relate it to an index of free radical activity in these patients. DESIGN:In vivo and in vitro indices of platelet function and diene conjugate molar ratios were measured in diabetic and...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.8.676
更新日期：1991-08-01 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:Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key compone...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvt265
更新日期：2014-03-01 00:00:00
abstract：:Sinoatrial conduction times, estimated by premature atrial stimulation, were compared with direct measurement of the sinoatrial conduction time in 15 isolated rabbit sinus node preparations before and after intrasinusal pacemaker shifts induced by cooling. Transmembrane potentials and surface electrograms were recorde...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/20.2.81
更新日期：1986-02-01 00:00:00
abstract：OBJECTIVE:Anisotropic conduction characteristics, which may be expressed as the ratio of conduction velocities in the longitudinal (Vlong) and transverse (Vtrans) fibre directions, have been shown to stabilise reentry and favour the induction of sustained, uniform ventricular tachycardia. The aim of this study was to i...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(96)88593-2
更新日期：1995-03-01 00:00:00
abstract：OBJECTIVE:It has been suggested that nitric oxide (NO) is involved in the regulation of myocardial function in a variety of diseases such as dilated cardiomyopathy, myocarditis, heart transplant rejection, and septic shock. However, the underlying mechanism of NO mediated reduction of cardiac contractility has not been...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00149-1
更新日期：1997-11-01 00:00:00
abstract：OBJECTIVES:The state of the vasodilator systems in congestive heart failure is poorly defined. Plasma atrial natriuretic peptide is increased, whereas endothelium derived relaxing factor activity can be decreased. Atrial natriuretic peptide and endothelium derived relaxing factor both cause vascular relaxation by gener...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/27.6.1094
更新日期：1993-06-01 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：:Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of mat...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2004.06.006
更新日期：2004-10-01 00:00:00
abstract：:Primary cardiomyopathy is an important cause of mortality in children and adults. Apart from inherited disorders of myocardial contractile and structural proteins, several defects of energy metabolism may cause cardiomyopathy. Most of the energy required for myocardial contraction is derived from aerobic metabolism. F...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/s0008-6363(97)00141-7
更新日期：1997-08-01 00:00:00
abstract：:The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by bi...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvs081
更新日期：2012-05-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00143-0
更新日期：1997-10-01 00:00:00
abstract：AIMS:Chronic pressure or volume overload induce concentric vs. eccentric left ventricular (LV) remodelling, respectively. Previous studies suggest that distinct signalling pathways are involved in these responses. NADPH oxidase-4 (Nox4) is a reactive oxygen species-generating enzyme that can limit detrimental cardiac r...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz331
更新日期：2021-01-01 00:00:00
abstract：:A mathematical formulation of the blood flow behaviour through a capillaron model is described. The formulation is applied to the analysis of post-occlusion (reactive) hyperaemia and autoregulation. ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/10.1.13
更新日期：1976-01-01 00:00:00
abstract：OBJECTIVES:We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS:Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left ante...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00316-7
更新日期：1998-04-01 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:Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mec...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvaa239
更新日期：2020-08-10 00:00:00
abstract：OBJECTIVE:The aim was to assess the significance of polymorphonuclear leucocytes on the myocardial capillary permeability to a small hydrophilic indicator, on the vascular tone of the resistance vessels, and on contractile function following ischaemia and reperfusion. METHODS:Open chest, anaesthetised dogs were random...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/27.7.1288
更新日期：1993-07-01 00:00:00
abstract：AIMS :Activation of the angiotensin (Ang)-(1-7)/Mas receptor (R) axis protects from sympathetic overactivity. Endocytic trafficking is an essential process that regulates receptor (R) function and its ultimate cellular responses. We investigated whether the blunted responses to Ang-(1-7) in hypertensive rats are associ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvz332
更新日期：2020-10-01 00:00:00
abstract：:This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts during the second half of the 20th century at a period where pressure measurements were the rule. Thinking flow instead of pressure dynamics corresponded to in-depth conceptual changes: whereas blood pressure generally has a single posit...
journal_title：Cardiovascular research
pub_type： 社论,历史文章
doi：10.1016/s0008-6363(01)00307-8
更新日期：2001-08-01 00:00:00
abstract：OBJECTIVE:The aim of the presented method was the characterization of different complex heart rate dynamics in conscious rabbits as well as during general anaesthesia and vagal blockade. This was done by non-linear prediction of original measured and special surrogate data in the phase space. METHOD:The development of...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end di...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/21.4.241
更新日期：1987-04-01 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：:A diminished sympathetic activity has been related to training bradycardia seen at rest and during exercise. In order to evaluate if changes in heart adrenergic receptors can be one of the mechanisms by which the sympathetic responsiveness could be decreased by physical training, the number and affinity of beta-adrene...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/16.9.530
更新日期：1982-09-01 00:00:00
abstract：OBJECTIVE:Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaem...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/28.3.312
更新日期：1994-03-01 00:00:00
abstract：:Studies were carried out in four different canine preparations to determine the effect of collateral flow on early changes induced by acute segmental ischaemia. The results of these experiments indicated that collateral flow provided a limited and variable amount of protection. When collateral flow was eliminated, myo...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/12.5.309
更新日期：1978-05-01 00:00:00
abstract：OBJECTIVE:At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：AIMS:It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis tha...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr167
更新日期：2011-11-01 00:00:00
abstract：STUDY OBJECTIVE:The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN:Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioliga...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.9.764
更新日期：1991-09-01 00:00:00
