Abstract:
Aims:Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however. Methods and results:To address this, a rat model of MI was employed to compare cardioprotective potentials (lower infarct size and improve post-ischemic function) of native FGF1 and an engineered FGF1 (FGF1ΔHBS) with reduced heparin-binding affinity when given at the onset of reperfusion in the absence or presence of heparin. FGF1 and FGF1ΔHBS did not alter heparin's anticoagulant properties. Treatment with heparin alone or native FGF1 significantly reduced infarct size compared to saline (P < 0.05). Surprisingly, treatment with FGF1ΔHBS markedly lowered infarct size compared to FGF1 (P < 0.05). Both native and modified FGF1 restored contractile and relaxation function (P < 0.05 versus saline or heparin). Furthermore, FGF1ΔHBS had greater improvement in cardiac function compared to FGF1 (P < 0.05). Heparin negatively impacted the cardioprotective effects (infarct size, post-ischemic recovery of function) of FGF1 (P < 0.05) but not of FGF1ΔHBS. Heparin also reduced the biodistribution of FGF1, but not FGF1ΔHBS, to the left ventricle. FGF1 and FGF1ΔHBS bound and triggered FGFR1-induced downstream activation of ERK1/2 (P < 0.05); yet, heparin co-treatment decreased FGF1-produced ERK1/2 activation, but not that activated by FGF1ΔHBS. Conclusion:These findings demonstrate that modification of the heparin-binding region of FGF1 significantly improves the cardioprotective efficacy, even in the presence of heparin, identifying a novel FGF ligand available for therapeutic use in ischemic heart disease.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Huang C,Liu Y,Beenken A,Jiang L,Gao X,Huang Z,Hsu A,Gross GJ,Wang YG,Mohammadi M,Schultz JEJdoi
10.1093/cvr/cvx165subject
Has Abstractpub_date
2017-11-01 00:00:00pages
1585-1602issue
13eissn
0008-6363issn
1755-3245pii
4107349journal_volume
113pub_type
杂志文章abstract:AIMS:It has been reported that laminar shear flow (LF) improves barrier functions in vascular endothelial cells (ECs), whereas disturbed flow (DF) impairs the barrier. Our previous study showed that LF stimulus led to the activation of the cysteine protease, m-calpain, in ECs, which can influence RhoA activity. We hypo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp311
更新日期:2010-02-01 00:00:00
abstract::Myocardial lactate content and simultaneous evolution of a lactate arteriovenous gradient associated with incomplete obstruction of the left coronary bed were studied in dog hearts. Samples of blood were taken from a peripheral artery and the coronary sinus; transmural samples of myocardial tissue were obtained from t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.10.552
更新日期:1982-10-01 00:00:00
abstract:AIMS:Although the use of drug-eluting stents (DESs) has been shown to limit neointima hyperplasia, currently available DESs may adversely affect re-endothelialization. To evaluate whether a novel gene silencer pyrrole-imidazole (PI) polyamide targeting transforming growth factor (TGF)-beta1 is a candidate agent for the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn355
更新日期:2009-03-01 00:00:00
abstract:AIM:Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm069
更新日期:2008-02-01 00:00:00
abstract::Matrix metalloproteinase (MMP)-2 belongs to a family of zinc-dependent proteases which are best known for their ability to proteolyse extracellular matrix proteins throughout the body, including the cardiovascular system. Increased MMP-2 activity has been demonstrated in myocardial ischaemia and reperfusion injury and...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp268
更新日期:2010-02-01 00:00:00
abstract::Elevated sympathetic activity changes renal function and accelerates the development of hypertension. Principles of sympatho-renal interactions in chronic hypertension are reviewed. Alterations in the ontogeny of the sympathetic nervous system and the kidney, inherited abnormalities in sensory receptor function and ex...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2003.11.024
更新日期:2004-02-01 00:00:00
abstract:AIMS:Vascular inflammation is a major atherogenic factor and Toll-like receptor (TLR) 2 ligands, including bacterial and serum lipoproteins, seem to be involved in atherogenesis. On this basis, we analysed the effect of lipoproteins and different lipid components on TLR2-dependent signalling. METHODS AND RESULTS:In TL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVE:Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. METHODS:Rat aortic endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00269-2
更新日期:2000-01-14 00:00:00
abstract:AIMS:Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a high...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn182
更新日期:2008-11-01 00:00:00
abstract::The development of the heart is a complex process during which different cell types progressively contribute to shape a four-chambered pumping organ. Over the last decades, our understanding of the specification and transcriptional regulation of cardiac development has been greatly augmented as has our understanding o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr078
更新日期:2011-07-15 00:00:00
abstract::Major advances in molecular biology over the past decade have increased our understanding of how genes are expressed and regulated in mammalian cells in vivo. This knowledge has been translated to investigations of the molecular and cellular biology of the cardiovascular system. Gene transfer, the introduction of a re...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/28.4.445
更新日期:1994-04-01 00:00:00
abstract::Arterial blood pressures were measured simultaneously in the thoracic and abdominal aortas in the same conscious rats. Intravenous administration of sodium nitroprusside caused a greater fall in systolic blood pressure in the abdominal aorta than in the thoracic aorta, whereas intravenous administration of methoxamine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.5.379
更新日期:1986-05-01 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:AIMS:n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq411
更新日期:2011-05-01 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:Inflammatory cells invade the fibrotic myocardium of spontaneously hypertensive rats at the same sites as where fibroblasts are produced. The role of these inflammatory cells in myocardial fibrogenesis was studied in the present work. METHODS:The production and distribution of proteins that may be implicated...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::The effect of adding fibrinolytic to penicillin therapy in experimentally induced streptococcal bacterial endocarditis has been studied in the rabbit. In 9 day old infected lesions, the vegetations could be substantially reduced in size after a 3 day course of intravenous streptokinase. Quantitative microbiological te...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.8.482
更新日期:1980-08-01 00:00:00
abstract:OBJECTIVE:The aim was to determine the relationship between the rate of reflow and vulnerability to reperfusion induced arrhythmias. METHODS:Isolated rat hearts, in which left and right coronary arteries were perfused independently, were subjected to transient (10 min) cessation of flow to the left coronary bed. Durin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.316
更新日期:1992-04-01 00:00:00
abstract:OBJECTIVE:To characterise the effect of coronary intra-arterial thrombosis upon the downstream vascular bed. BACKGROUND:The vascular response downstream from a coronary intra-arterial thrombus has not previously been characterised. We postulated that downstream vasoconstriction might result from the presence of endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Activation of sphingosine kinase/sphingosine-1-phosphate (SK/S1P)-mediated signalling has been recognized as critical for cardioprotection in response to acute ischaemia/reperfusion injury. Incubation of S1P with cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischaemia or ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn309
更新日期:2009-05-01 00:00:00
abstract:AIMS:The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic disease...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw172
更新日期:2016-10-01 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::The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.570
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVE:Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+(ATP)) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+(ATP) channels. METHODS:Guinea pig ventricular myocytes were isolated using collagenase digestion....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00092-8
更新日期:1997-08-01 00:00:00
abstract::This review focuses on the genomic response following a preconditioning stimulus. Initial studies demonstrated that classical ischemic preconditioning mediated by cyclic episodes of short durations of reversible ischemia and reperfusion could result in the reprogramming of gene expression. Some of these genes are tran...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.02.023
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVES:The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. METHODS:Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:Rapid ventricular pacing reliably induces severe congestive heart failure in dogs, with an associated attenuation of baroreflex sensitivity. Unique to this model is the capacity for rapid recovery of haemodynamics and plasma noradrenaline following the cessation of pacing; however, whether baroreflex sensitiv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.384
更新日期:1994-03-01 00:00:00
abstract::There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Bloo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.12.734
更新日期:1985-12-01 00:00:00
abstract::Electrophysiologic remodeling is a process whereby heart disease alters the electrophysiologic properties of cardiac tissue. These alterations, in turn, can cause or exacerbate disease-related arrhythmias. Ion channels are the fundamental molecular units underlying cardiac electrophysiology, and it therefore follows t...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00063-2
更新日期:1999-05-01 00:00:00
abstract:OBJECTIVE:Previous studies have shown that cardiac protection by ischaemic preconditioning wanes before contractile function recovers; thus stunning is insufficient to cause preconditioning. To test whether reduced contractile effort is necessary for preconditioning induced protection, the effect on myocardial infarct ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.4.585
更新日期:1993-04-01 00:00:00