Abstract:
:Sirtuin 3 (Sirt3) is an NAD(+)-dependent mitochondrial deacetylase associated with superoxide dismutase 2 (SOD2)-mediated protection from oxidative stress. We have reported accelerated weight gain and impaired metabolic flexibility in atherosclerotic Sirt3 (-/-) mice. Oxidative stress is a hallmark of endothelial dysfunction. Yet, the role of Sirt3 in this context remains unknown. Thus, we aimed to unravel the effects of endogenous Sirt3 on endothelial function and oxidative stress. Knockdown of Sirt3 in human aortic endothelial cells (HAEC) increased intracellular mitochondrial superoxide accumulation, as assessed by electron spin resonance spectroscopy and fluorescence imaging. Endothelium-dependent relaxation of aortic rings from Sirt3 (-/-) mice exposed to a normal diet did not differ from wild-type controls. However, following 12 weeks of high-cholesterol diet and increasing oxidative stress, endothelial function of Sirt3 (-/-) mice was mildly impaired compared with wild-type controls. Relaxation was restored upon enhanced superoxide scavenging using pegylated superoxide dismutase. Knockdown of Sirt3 in cultured HAEC diminished SOD2 specific activity, which was compensated for by a CCAAT/enhancer binding protein beta (C/EBP-β)-dependent transcriptional induction of SOD2. Abrogation of this feedback regulation by simultaneous knockdown of C/EBP-β and Sirt3 exacerbated mitochondrial superoxide accumulation and culminated into endothelial cell death upon prolonged culture. Taken together, Sirt3 deficiency induces a mild, superoxide-dependent endothelial dysfunction in mice fed a high-cholesterol diet. In cultured endothelial cells, a novel C/EBP-β-dependent rescue mechanism maintains net SOD2 activity upon transient knockdown of Sirt3.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Winnik S,Gaul DS,Siciliani G,Lohmann C,Pasterk L,Calatayud N,Weber J,Eriksson U,Auwerx J,van Tits LJ,Lüscher TF,Matter CMdoi
10.1007/s00395-016-0552-7subject
Has Abstractpub_date
2016-05-01 00:00:00pages
33issue
3eissn
0300-8428issn
1435-1803pii
10.1007/s00395-016-0552-7journal_volume
111pub_type
杂志文章abstract::Protection from postconditioning has been documented in in situ animal models and it has been proposed that it is targeting circulating leukocytes. We therefore tested whether postconditioning can protect leukocyte-free, buffer-perfused rabbit hearts. Infarct size was measured with triphenyltetrazolium staining. In co...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-004-0498-4
更新日期:2005-01-01 00:00:00
abstract::There is no doubt that major advances have been made in cardiac electrophysiology using single heart cells. Accurate analysis of rapid inward sodium current and the second inward current carried by calcium has resulted in a major re-examination of the steps involved in excitation-contraction coupling in the heart. Fut...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-662-11041-6_17
更新日期:1985-01-01 00:00:00
abstract::There is a growing need for pharmacological agents to manage cardiovascular disease in the rapidly growing elderly population. Here, we determine if acetaminophen is efficacious in decreasing age-related increases in cardiac reactive oxygen species (ROS) and apoptosis in aging Fischer 344 X Brown Norway rats. Compared...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-010-0094-3
更新日期:2010-07-01 00:00:00
abstract::Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibrob...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-011-0181-0
更新日期:2011-09-01 00:00:00
abstract::Sarcoplasmic reticulum (SR) from left ventricles of rats that developed spontaneous hypertension was studied in vitro. Similar increases of left ventricular mass were found when grouping the animals into mild and severe hypertensives (average systolic arterial pressure of 168 +/- 4 and 202 +/- 6 mmHg, respectively). T...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907362
更新日期:1988-05-01 00:00:00
abstract::Ventricular remodeling following nonfatal myocardial infarction includes an excentric hypertrophy of the surviving myocardium, associated with hemodynamic overload. Disseminated cardiomyocyte apoptosis and phenotype changes of the surviving myocardium, such as a labile calcium homeostasis of the hypertrophied cardiomy...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050228
更新日期:1998-01-01 00:00:00
abstract::The authors have retracted this article [1] because of modifications in the control lanes of Figs. 2a and 8a of the COX1 blot obtained for 18-week-old rats (rotation, horizontal flipping and re-use of the control lanes for the 35-week-old rats blot). In light of the concerns raised, the conclusions drawn in this artic...
journal_title:Basic research in cardiology
pub_type: 杂志文章,撤回出版物
doi:10.1007/s00395-018-0680-3
更新日期:2018-04-18 00:00:00
abstract::Alterations in myocardial membrane phospholipids may play an important role in the pathogenesis of ischaemic myocardial cell injury. Studies in canine myocardium, perfused rat heart, and cultured myocardial cells have demonstrated that the accumulation of free arachidonic acid correlates with the development of irreve...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-662-08390-1_15
更新日期:1987-01-01 00:00:00
abstract::32 patients were studied by His-bundle recordings to examine the extent to which frequency and autonomic nervous system influence the conduction velocity in the subdivisions (atrium, AV-node, His-Purkinje system) of the normal PR-interval. The measurements were performed during sinus rhythm and three electrically indu...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::The effect of 0.1 mg/kg Verapamil on the extent of the ischemic area following ligation of a branch of the left descending coronary artery was studied in anesthetized open chest dogs. The sum of the ST-segment elevation during the entire period of occlusion in the epicardial ECG was 15 mV in control infarction compare...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01905620
更新日期:1975-03-01 00:00:00
abstract::The influence of decapitation, ketamine and thiopental anesthesia on some properties of rat heart mitochondria was compared. Polarographic analysis were performed, oxygen consumption rates, respiratory control index, ADP : O ratio and oxidation of exogenous NADH were determined. Electronmicroscopic and gasometric exam...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907952
更新日期:1981-03-01 00:00:00
abstract::The ability of the rhesus monkey to form coronary collaterals was tested in ten animals. Ameroid constrictors were implanted on the left circumflex coronary artery and allowed to remain for 12 weeks. One animal died of an acute myocardial infarction nine days after surgery; the remaining animals survived without clini...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906462
更新日期:1983-09-01 00:00:00
abstract:OBJECTIVES:The impact of acute collagen disruption by the disulfide donor, 5,5'-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts. METHODS:Collagen was degraded acutely in 13 isolated, isovolumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788632
更新日期:1997-06-01 00:00:00
abstract::The pathogenesis and progression of hypertensive heart disease are unclear; however, both involve a genetic predisposition and environmental influences. To test the role of exogenous factors, we examined the hearts of spontaneously hypertensive rats (SHR) exposed to noise stress and ethanol intake. Twenty-two SHR and ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00794951
更新日期:1994-11-01 00:00:00
abstract::Rate or frequency-dependence is a characteristic property of antiarrhythmic drugs belonging to the Vaughan William classes I and III. The rate-dependence of class I drugs (i.e., increasing blockade of fast Na(+)-channels with faster rates) results from periodical drug binding to Na(+)-channel sites which are preferabl...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050236
更新日期:1998-01-01 00:00:00
abstract::Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into contr...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0750-1
更新日期:2019-09-09 00:00:00
abstract::In this paper, we review the hypothesis that activated tissue renin-angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue renin-angiotensin systems behave functionally distinct from the circulating renin-angiotensin system; b) tissue renin-angiotensin s...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/BF00795368
更新日期:1996-01-01 00:00:00
abstract::Atherosclerotic coronary arteries are more calcified in patients with than without chronic kidney disease (CKD). We addressed the potential for coronary microvascular obstruction in patients with and without CKD during stenting for saphenous vein aorto-coronary graft (SVG) stenosis under protection with a distal occlu...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0303-3
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:The clinical usefulness of class III antiarrhythmic drugs for the treatment of tachyarrhythmias is limited by their potential proarrhythmic effects, mainly torsades-depointes (TdP). The goal of this experimental study was to develop an isolated whole-heart model exhibiting typical characteristics of class III...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050073
更新日期:1998-04-01 00:00:00
abstract::Reversibly injured myocardium after short periods of ischemia is characterized by a prolonged depression of contractile function which can, however, be enhanced by inotropic interventions. Thus, a lack of inotropic stimulation due to ischemic damage of cardiac sympathetic nerves has been suggested as a mechanism under...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-662-11038-6_22
更新日期:1990-01-01 00:00:00
abstract::The clinical use of positive inotropic agents has been associated with increased mortality, with proarrhythmia speculated to be a contributing factor. This study compares the arrhythmogenic potentials of six positive inotropic agents representing different mechanistic classes: the beta-adrenergic agonist dobutamine, t...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050181
更新日期:2000-06-01 00:00:00
abstract::An ischaemia-like state in cultured heart cells has been obtained by markedly restricting the volume of extracellular medium combined with total deprivation of oxygen (anoxia) and glucose. Cellular injury, as reflected by the release of both cytoplasmic and lysosomal enzymes was significantly greater than during anoxi...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::A model of vascular endothelial cell is proposed to describe the mechanisms by which cytosolic calcium (Cai) is modulated and endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) are released when the cell is stimulated by agonist. The intracellular Ca2+ store of the model cell is comprised of a superfic...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00796518
更新日期:1992-07-01 00:00:00
abstract::The cardiac renin angiotensin system (RAS) is the target for number of therapeutic interventions which proved successful in heart failure. Angiotensin converting enzyme (ACE) inhibitors belong to the most efficient strategies available and angiotensin receptor (ATR) antagonists may be comparably effective. The direct ...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050207
更新日期:1998-01-01 00:00:00
abstract::To understand the effect of transcription regulation in modulating cardiac aging, we sought to study the role of serum response factor (SRF), a key transcription factor in the heart that is normally increased with senescence and also in congestive heart failure. A Tet-Off gene expression system was used for cardiac-sp...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-006-0634-z
更新日期:2007-05-01 00:00:00
abstract::We tested the hypothesis that isoproterenol would increase myocardial work and O2 consumption at reduced efficiency and that both left ventricular hypertrophy and chemical sympathectomy would lead to changes in this myocardial efficiency response. Left ventricular hypertrophy was produced by aortic valve plication in ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00789303
更新日期:1996-07-01 00:00:00
abstract::The influence of perfusion pressure (5-8 kPa) on coronary flow and myocardial Ca2+-washout during Ca2+-free perfusion, and on the occurrence of calcium paradox after subsequent Ca2+-reperfusion, was studied in isolated, stimulated, rat heart ventricles. During the Ca2+-free perfusion period (3 min) the following chang...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907580
更新日期:1980-03-01 00:00:00
abstract::Cardiac mass, cell size and capillary supply were studied in the hearts of spontaneously hypertensive rats (SHR) and compared to genetically similar non-hypertensive Wistar-Kyoto (WKY) of three adult ages: 5, 15 and 23 months. The left ventricular weight of SHR was not significantly greater than that of WKY at 5 month...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908138
更新日期:1984-07-01 00:00:00
abstract::The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in w...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908307
更新日期:1984-03-01 00:00:00
abstract::Elucidation of the subcellular mechanism of myocardial ischemic preconditioning should be facilitated by precise knowledge of the biology of the cardioprotective response. Any proposed molecular mechanism for preconditioning must be initiated during the required ischemic stress period. The studies reported in this pap...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00805571
更新日期:1997-04-01 00:00:00