Abstract:
:Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with better benefit-risk profiles and for safer anticoagulants for existing and new indications. The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.
journal_name
Circ Resjournal_title
Circulation researchauthors
Chan NC,Weitz JIdoi
10.1161/CIRCRESAHA.118.313155subject
Has Abstractpub_date
2019-02-01 00:00:00pages
426-436issue
3eissn
0009-7330issn
1524-4571journal_volume
124pub_type
杂志文章,评审abstract::Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I-III) or saline (controls) (group IV) was ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.54.3.277
更新日期:1984-03-01 00:00:00
abstract::We designed this study to test the hypothesis that in acute mitral regurgitation the mitral regurgitant area (MRA) is a dynamic quantity which varies with the time variation of ventricular volume. Mitral insufficiency was created in five open-chest dogs in which a portion of the anterior leaflet was excised. Phasic ao...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.5.677
更新日期:1979-11-01 00:00:00
abstract::Recent evidence suggests that functional diversity of vascular smooth muscle is produced in part by a differential expression of ion channels. The aim of the present study was to examine the role of Ca(2+)-activated K(+) channels (K(Ca) channels) in the expression of smooth muscle cell functional phenotype. We found t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.9.e33
更新日期:1999-10-29 00:00:00
abstract::Electrotonic coupling of cardiac myocytes at gap junctions may influence patterns of conduction in myocardium. To delineate the three-dimensional structure and distribution of intercellular junctions, we analyzed serial ultrathin sections of canine myocardium with transmission electron microscopy and disaggregated myo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.3.563
更新日期:1989-03-01 00:00:00
abstract::We recently showed that the transient expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the G protein alpha(q) subunit (HAalpha(q)*) in the hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after HAalpha(q)* protein becomes u...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.11.1085
更新日期:1999-11-26 00:00:00
abstract::The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n = 11) or a 15-second occlusion at 4-minute intervals (group 2, n = 7) were repeated day and nig...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.2.287
更新日期:1989-02-01 00:00:00
abstract::The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-depend...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000253900.66640.34
更新日期:2007-01-05 00:00:00
abstract::A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription fac...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000127122.22685.0A
更新日期:2004-05-14 00:00:00
abstract::Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained u...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.10.929
更新日期:2000-11-10 00:00:00
abstract::Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiograph...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000016960.61087.86
更新日期:2002-05-03 00:00:00
abstract::During an investigation of the effect of ryanodine on contractions in cardiac muscle, it was found that long rest periods removed all or most of the drug's effect. Therefore, we studied the kinetics of block development and recovery from block produced by low concentrations of ryanodine (1-100 pM) on the postrest cont...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.4.560
更新日期:1987-04-01 00:00:00
abstract::Many members of the two-pore-domain potassium (K(+)) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whether I(KAA), a background K(+) current activated by negative pressure (stretch) and by arachidonic acid (AA) and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1601.094979
更新日期:2001-08-17 00:00:00
abstract::3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000097262.21507.DF
更新日期:2003-10-17 00:00:00
abstract::To test the hypothesis that early interventional treatment with insulin-like growth factor-1 (IGF-1) alleviates subsequent development of dilated cardiomyopathy, cardiac-specific IGF-1 expression was introduced by selective cross-breeding into a transgenic mouse model of heart failure that displays phenotypic characte...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000013780.77774.75
更新日期:2002-04-05 00:00:00
abstract:RATIONALE:Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear. OBJECTIVES:This study sought to examine the associations between social...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309443
更新日期:2017-06-09 00:00:00
abstract::The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.6.1097
更新日期:1994-06-01 00:00:00
abstract::Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also show...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000266970.34017.8d
更新日期:2007-05-11 00:00:00
abstract:RATIONALE:Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304164
更新日期:2014-10-10 00:00:00
abstract:RATIONALE:Plasminogen activator inhibitor-1 (PAI-1) is a biomarker for several vascular disease states; however, its target of action within the vessel wall is undefined. OBJECTIVE:Determine the ability of PAI-1 to regulate myoendothelial junction (MEJ) formation. METHODS AND RESULTS:MEJs are found throughout the vas...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.215723
更新日期:2010-04-02 00:00:00
abstract::In patients with congestive heart failure, skeletal muscle is characterized by a smaller proportion of slow-twitch oxidative fibers and reduced oxidative enzyme activity. However, whether these changes result from disuse or occur as a direct consequence of heart failure is unresolved. To address this issue, 18 rats wi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.1.128
更新日期:1996-07-01 00:00:00
abstract::The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.2.172
更新日期:1977-08-01 00:00:00
abstract::Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be contr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1608
更新日期:1991-12-01 00:00:00
abstract:RATIONALE:Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311194
更新日期:2018-02-02 00:00:00
abstract::A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.8
更新日期:1975-01-01 00:00:00
abstract::The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192443
更新日期:2009-07-02 00:00:00
abstract::Previous studies have postulated an important role for the inwardly rectifying potassium current (I(K1)) in controlling the dynamics of electrophysiological spiral waves responsible for ventricular tachycardia and fibrillation. In this study, we developed a novel tissue model of cultured neonatal rat ventricular myocy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.178335
更新日期:2009-02-13 00:00:00
abstract::Cells with endothelial phenotype generated from adult peripheral blood have emerging diagnostic and therapeutic potential. This study examined the lineage relationship between, and angiogenic function of, early endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) in culture. Culture conditio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000105569.77539.21
更新日期:2003-11-28 00:00:00
abstract:RATIONALE:ATP-binding cassette transporter A1 (ABCA1) plays a critical role in eliminating excess free cholesterol from tissues by effluxing cellular free cholesterol and phospholipids to lipid-poor apolipoprotein AI. Macrophage ABCA1 also dampens proinflammatory myeloid differentiation primary-response protein 88-depe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.269043
更新日期:2012-11-09 00:00:00
abstract::We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.600
更新日期:1995-04-01 00:00:00
abstract:RATIONALE:Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. OBJECTIVE:To measure lncRNAs in patients with myocardi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.303836
更新日期:2014-09-12 00:00:00