Abstract:
:Conventional antithrombotic treatments with antiplatelet, anticoagulant or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive because of its unique ability to express an antithrombotic gene at selected sites of the vessel wall (where thrombosis is threatened) while avoiding systemic anticoagulation. Clinical conditions potentially amenable to antithrombotic gene therapy include coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, peripheral artery angioplasty or thrombectomy, intravascular stenting, and vascular graft prostheses. Gene therapy may prove effective in preventing subacute thrombosis in these settings and, eventually, may play an adjuvant role to systemic thrombolysis in the treatment of acute arterial occlusion. The introduction of an antithrombotic gene into the arterial wall can be achieved either by direct in vivo gene transfer (e.g., by luminal administration of a viral vector) or by in vitro genetic manipulation of cells before their seeding onto vascular grafts, stents, or denuded arteries. The direct gene transfer approach has been used to deliver antithrombotic genes to animal arteries in vivo. Antithrombotic genes used to date include those encoding enzymes of the prostacyclin synthetic pathway, nitric oxide synthase, the thrombin inhibitor hirudin, and thrombomodulin. The in vitro gene transfer approach has been used to enhance the fibrinolytic activity of vascular grafts by overexpressing plasminogen activators. If the initial successes of gene therapy for thrombotic disease in animal models are confirmed by longer-term experiments, and if new vectors are developed which permit prolonged transgene expression without inflammation, human studies can be initiated.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Vassalli G,Dichek DAdoi
10.1016/s0008-6363(97)00153-3subject
Has Abstractpub_date
1997-09-01 00:00:00pages
459-69issue
3eissn
0008-6363issn
1755-3245pii
S0008-6363(97)00153-3journal_volume
35pub_type
杂志文章,评审abstract:OBJECTIVES:Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation. METHODS AND RESULTS:Forty patients with de novo presentatio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.05.003
更新日期:2007-09-01 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:AIMS:This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta. METHODS AND RESULTS:Aortic segments from orchidectomized and control male Sprague-Dawley ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm059
更新日期:2008-02-01 00:00:00
abstract:AIMS:The regulation of vascular diameter by vasoconstrictors and vasodilators requires that vascular smooth muscle cells (VSMCs) be physically coupled to extracellular matrix (ECM) and neighbouring cells in order for a vessel to mechanically function and transfer force. The hypothesis was tested that integrin-mediated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs239
更新日期:2012-10-01 00:00:00
abstract::Labetolol, which blocks both alpha and beta-adrenoceptors, was found to have direct actions on cardiac muscle which could themselves be antiarrhythmic. It depressed the maximum rate of depolarisation, and reduced conduction velocity, in atrial and ventricular muscle and in Purkinje cells, implying restriction of fast ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.5.233
更新日期:1982-05-01 00:00:00
abstract::The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptor...
journal_title:Cardiovascular research
pub_type: 评论,杂志文章,评审
doi:10.1016/s0008-6363(99)00319-3
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00036-4
更新日期:1998-06-01 00:00:00
abstract:AIMS:Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that a...
journal_title:Cardiovascular research
pub_type: 杂志文章,随机对照试验
doi:10.1093/cvr/cvw089
更新日期:2016-07-01 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:AIMS:In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw091
更新日期:2016-07-01 00:00:00
abstract::The role of mediators of inflammation in the pathogenesis and evolution of myocardial infarction has attracted increased interest as interventions which inhibit the inflammatory response after coronary artery occlusion have been shown to decrease infarct size. The distribution of fibrinogen and albumin in ischaemia my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.1.36
更新日期:1986-01-01 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::In the heart, Ca(2+) influx via Ca(V)1.2 L-type calcium channels (LTCCs) is a multi-functional signal that triggers muscle contraction, controls action potential duration, and regulates gene expression. The use of LTCC Ca(2+) as a multi-dimensional signalling molecule in the heart is complicated by several aspects of ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvt021
更新日期:2013-05-01 00:00:00
abstract::The cardiospecificity of the MB isoenzyme of creatine kinase, EC 2.7.3.2, (CK) with its associated diagnostic and research value has resulted in the development of a number of procedures for the separation and quantitation of the three isoenzymes of CK. In our experience methods involving cellulose acetate electrophor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.94
更新日期:1977-03-01 00:00:00
abstract:OBJECTIVE:Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.006
更新日期:2005-09-01 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:OBJECTIVE:The aim of this study is to investigate the idea that altered fibroblast contractile activity is involved in the pathogenesis of hypertensive heart disease (HHD). METHODS:Cell area and contraction are quantified using the traction force microscopy technique for cardiac fibroblasts isolated from both normoten...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.09.021
更新日期:2003-12-01 00:00:00
abstract:OBJECTIVE:Both superoxide dismutase (SOD) and nitric oxide synthase (NOS) have been implicated in delayed preconditioning (DP) to ischemia/reperfusion (I/R) in the heart. We used isolated cardiac myocytes to test the hypothesis that SOD and NOS may interact in the development of DP. METHODS:Mouse neonatal cardiac myoc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00502-9
更新日期:2003-10-01 00:00:00
abstract::In order to evaluate clinically recorded jugular vein pulses it is necessary to understand the transmission process of the right atrial pressure pulse through the caval veins up to the jugular veins. The transmission speed at distinct points of the venous pressure curve was studied in the superior vena cava of 20 anae...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.10.627
更新日期:1983-10-01 00:00:00
abstract:OBJECTIVE:Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS:Right atrial appendages were obtained from eight patients with paroxysmal AF, ten ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00045-0
更新日期:1999-05-01 00:00:00
abstract::We used the phase modulated rotating frame imaging technique to measure transmural distribution of phosphorus metabolites in 10 anaesthetised ventilated pigs using a double surface coil placed on the surface of the left ventricle. Anaesthesia was maintained in five animals with halothane, barbiturate and nitrous oxide...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.12.1015
更新日期:1989-12-01 00:00:00
abstract::The effect of digoxin, at two different inotropic levels, was examined in normo- and hyperkalaemic dogs. For similar inotropic responses, normo- and hyperkalaemic dogs had similar levels of (Na+, K+)-ATPase inhibition and microsomal-bound digoxin. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.4.515
更新日期:1975-07-01 00:00:00
abstract:AIMS:Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz136
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVES:Myocardial ischemia results in an early phase of arrhythmias that primarily involves reentrant mechanisms. However, the trigger that initiates reentry remains unknown. We studied the initiation of reentry attending the development of electrical heterogeneity during simulated ischemia in isolated canine right...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The effect of chronic propranolol administration (2 mg.kg-1.d-1 for 14d) and withdrawal on microvascular perfusion was studied in rabbit myocardium. Fluorescein isothiocyanate-dextran was injected into four groups of anaesthetised open chest rabbits. Fluorescent microscopy was used to identify the perfused vessels and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.11.793
更新日期:1988-11-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects. METHODS:Transmembrane action potentials and electrograms were recorded fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.11.1662
更新日期:1994-11-01 00:00:00
abstract:AIMS:Atherogenesis, evolution of plaque, and outcomes following endovascular intervention depend heavily on the unique vascular architecture of each individual. Patient-specific, multiscale models able to correlate changes in microscopic cellular responses with relevant macroscopic flow, and structural conditions may h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu124
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:The heart contains proteins of the annexin family, a unique group of calcium binding proteins. This study was aimed at identifying the major cardiac annexins and determining their distribution in the rat heart. METHODS:Annexins were isolated by affinity chromatography and purified by ion exchange high pressu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.7.1359
更新日期:1993-07-01 00:00:00
abstract:AIMS:In cardiomyocytes, protein kinase D1 (PKD1) plays a central role in the response to stress signals. From a yeast two-hybrid assay, we have identified Enigma Homolog 1 (ENH1) as a new binding partner of PKD1. Since in neurons, ENH1, associated with protein kinase Cepsilon, was shown to modulate the activity of N-ty...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn052
更新日期:2008-06-01 00:00:00
abstract::We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular ca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1758
更新日期:1993-10-01 00:00:00