Abstract:
AIMS:Diabetes impinges upon mechanisms of cardiovascular repair. However, the biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains largely unknown. Here, we investigate the molecular targets of high glucose-induced damage in cardiac progenitor cells (CPCs) from murine and human hearts and attempt safeguarding CPC viability and function through reactivation of the pentose phosphate pathway. METHODS AND RESULTS:Type-1 diabetes was induced by streptozotocin. CPC abundance was determined by flow cytometry. Proliferating CPCs were identified in situ by immunostaining for the proliferation marker Ki67. Diabetic hearts showed marked reduction in CPC abundance and proliferation when compared with controls. Moreover, Sca-1(pos) CPCs isolated from hearts of diabetic mice displayed reduced activity of key enzymes of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD), and transketolase, increased levels of superoxide and advanced glucose end-products (AGE), and inhibition of the Akt/Pim-1/Bcl-2 signalling pathway. Similarly, culture of murine CPCs or human CD105(pos) progenitor cells in high glucose inhibits the pentose phosphate and pro-survival signalling pathways, leading to the activation of apoptosis. In vivo and in vitro supplementation with benfotiamine reactivates the pentose phosphate pathway and rescues CPC availability and function. This benefit is abrogated by either G6PD silencing by small interfering RNA (siRNA) or Akt inhibition by dominant-negative Akt. CONCLUSION:We provide new evidence of the negative impact of diabetes and high glucose on mechanisms controlling CPC redox state and survival. Boosting the pentose phosphate pathway might represent a novel mechanistic target for protection of CPC integrity.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Katare R,Oikawa A,Cesselli D,Beltrami AP,Avolio E,Muthukrishnan D,Munasinghe PE,Angelini G,Emanueli C,Madeddu Pdoi
10.1093/cvr/cvs291subject
Has Abstractpub_date
2013-01-01 00:00:00pages
55-65issue
1eissn
0008-6363issn
1755-3245pii
cvs291journal_volume
97pub_type
杂志文章abstract::Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery...
journal_title:Cardiovascular research
pub_type: 社论,评审
doi:10.1016/s0008-6363(98)00244-2
更新日期:1998-12-01 00:00:00
abstract::This study concerns the longterm effects of both epicardial and endocardial cryosurgery with particular reference to the coronary arteries. Sheep were subjected to epicardial cryosurgery without cardiopulmonary bypass, and to endocardial application with bypass. In both groups the heart was kept beating throughout the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.2.61
更新日期:1983-02-01 00:00:00
abstract:AIM:To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed. METHODS:ET-1 (0.013 microg/min) was infused to male ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00657-0
更新日期:2003-01-01 00:00:00
abstract:AIMS:Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that contributes to pathogenic cardiac remodelling via mechanisms that involve oxidative stress. However, the direct impact of TGF-beta1 on contractile function of ventricular myocytes is incompletely understood. METHODS AND RESULTS:Reacti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm022
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:The multifunctional Ca2+-binding protein S100A4 (also known as Mts1 and Fsp1) is involved in fibrosis and tissue remodeling in several diseases including cancer, kidney fibrosis, central nervous system injury, and pulmonary vascular disease. We previously reported that S100A4 mRNA expression was increased in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.03.027
更新日期:2007-07-01 00:00:00
abstract::Data from experiments in isolated cardiac muscle preparations indicate that adenosine in high concentration (10(-3) mol X litre-1) exerts a negative inotropic effect on the myocardium under basal conditions. The following study was performed to test the hypothesis that adenosine exerts a similar negative inotropic eff...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.4.220
更新日期:1984-04-01 00:00:00
abstract:OBJECTIVE:Automatic analysis of the frequency content of the fibrillatory baseline on the surface ECG accurately reflects the average rate of atrial fibrillation (AF). This frequency measurement correlates with the behavior of AF and predicts the response to administration of ibutilide, a new antiarrhythmic drug. Neith...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00156-x
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVE:The sequelae of myocardial ischaemia can in principle be alleviated by repeated reperfusion, but the accumulation of adenosine monophosphate (AMP) and the loss of interstitial adenosine may lead to adenylate depletion. Repeated oxidative stress could predispose the heart to reperfusion injury. The aim of this...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.5.502
更新日期:1992-05-01 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:It was our aim to investigate effects of human LDL, copper-, or AAPH-oxidized over different periods of time to different degrees (ox-LDL), on viability and electrophysiological parameters of isolated ventricular myocytes of guinea pigs. METHODS:Guinea pig ventricular myocytes were incubated with ox-LDL or n...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.009
更新日期:2005-04-01 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:AIMS:Smad7 plays a negative regulatory role in many inflammatory diseases, but its effect on hypertensive disease remains unknown. The present study tested the hypothesis that overexpression of Smad7 may have therapeutic potential for angiotensin II (Ang II)-mediated hypertensive cardiac remodelling. METHODS AND RESUL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt151
更新日期:2013-09-01 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:Cardiac parasympathetic nerve activity is reduced in most cardiovascular disease states, and this may contribute to enhanced cardiac sympathetic responsiveness. Disruption of inhibitory G-proteins (Gi) ablates the cholinergic pathway and increases cardiac endothelial nitric oxide (NO) synthase (eNOS) expressi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.04.034
更新日期:2005-09-01 00:00:00
abstract::Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.03.029
更新日期:2008-03-01 00:00:00
abstract::Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, t...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs111
更新日期:2012-07-15 00:00:00
abstract:OBJECTIVE:The aim was to examine whether an absolute reduction in energy supply is required for preconditioning against myocardial infarction, and whether an episode of increased adrenergic activity with or without supply-demand imbalance is capable of triggering cardioprotection. METHODS:41 anaesthetised dogs were su...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.11.2071
更新日期:1993-11-01 00:00:00
abstract::In pulmonary arterial hypertension (PAH), right ventricular (RV) adaptation is essential to overcome the chronic increases in RV pressure overload. Ultimately, RV compensatory mechanisms are not sufficient and patients succumb to RV failure. The processes underlying the transition of RV adaptation to RV failure are no...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvx145
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt269
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract:OBJECTIVE:Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. ME...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.10.019
更新日期:2005-02-15 00:00:00
abstract:OBJECTIVES:Early thrombolysis can reduce infarct size and enhance the long term recovery of contractile function after acute myocardial infarction. These benefits of early reperfusion may be confounded, however, by platelet mediated reocclusion after initial lysis, and "reperfusion injury" mediated by oxygen derived fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.925
更新日期:1993-06-01 00:00:00
abstract:OBJECTIVE:The aim was to clarify the roles of left atrial pressure and ventricular function in the determination of early diastolic filling. METHODS:Various grades of ventricular dysfunction were made in 12 mongrel dogs by coronary microembolization under pentobarbitone anaesthesia. Left atrial pressure was altered by...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.2.109
更新日期:1992-02-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to study the interactions between pulmonary capillary wedge pressure (an estimate of left atrial pressure), left atrial dimension, and atrial natriuretic factor during evolving heart failure. DESIGN:Sequential simultaneous measurements of haemodynamic variables, left atrial dimension, and p...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.7.570
更新日期:1990-07-01 00:00:00
abstract:OBJECTIVE:Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect again...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.01.024
更新日期:2004-06-01 00:00:00
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:OBJECTIVE:To study the intracellular pathways which mediate the inhibitory actions of adenosine on isoprenaline-stimulated calcium current (ICa) in atrioventricular (AV) nodal myocytes. METHODS:The whole-cell patch-clamp technique was used to record ICa from rabbit AV nodal cells, isolated by enzymatic and mechanical ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00043-6
更新日期:1997-05-01 00:00:00
abstract::The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00086-9
更新日期:2000-08-18 00:00:00
abstract::Muscle tissue in atrioventricular (A-V) cardiac valve leaflets was studied in 35 human hearts and was found to be more prominent in the anterior leaflet of the mitral (MAL) than in the other valve leaflets. From serial sectioning and wax model reconstruction, the anatomic arrangement of the muscle in the MAL indicates...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.11.675
更新日期:1978-11-01 00:00:00
abstract:OBJECTIVE:The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of thi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.6.847
更新日期:1994-06-01 00:00:00