Abstract:
OBJECTIVE:Experimental evidence suggests that modulation of myocardial substrate metabolism can markedly affect the progression of chronic heart failure (HF). We tested whether the inhibition of carnitine palmitoyl transferase-I (CPT-I), the enzyme regulating mitochondrial fatty acid oxidation, slows left ventricular remodeling and deterioration of function in pacing-induced HF. METHODS:Normal dogs (n=9) were compared to untreated dogs with pacing-induced HF (n=9) and HF dogs treated with 65 mg/kg/day of oxfenicine (HF+Oxf, n=9), a CPT-I inhibitor. RESULTS:HF+Oxf reached terminal failure (LV end-diastolic pressure=25 mm Hg) 6 days later than untreated HF (P<0.05). At 28 days of pacing, hemodynamic alterations and LV dilation were significantly attenuated and the 25% decrease in LV wall thickness was completely prevented in HF+Oxf vs. untreated HF, as was the activation of matrix metalloproteinase-2 and -9, markers of tissue remodeling. Oxfenicine also prevented HF-induced transcriptional down-regulation of CPT-I, medium chain acyl-CoA dehydrogenase, GAPDH and citrate synthase, key enzymes of cardiac energy metabolism. In addition, mRNA, but not protein levels of the nuclear receptor peroxisome proliferator-activated receptor-alpha were reduced in untreated HF, while they did not change significantly in HF+Oxf, as compared to control. CONCLUSIONS:CPT-I inhibition early in the development of HF prevented LV wall thinning and delayed the time to end-stage failure. While these results are limited to an experimental model of disease, they nevertheless suggest that CPT-I inhibition might be effective for slowing the progression of clinical HF.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Lionetti V,Linke A,Chandler MP,Young ME,Penn MS,Gupte S,d'Agostino C,Hintze TH,Stanley WC,Recchia FAdoi
10.1016/j.cardiores.2005.02.004subject
Has Abstractpub_date
2005-06-01 00:00:00pages
454-61issue
3eissn
0008-6363issn
1755-3245pii
S0008-6363(05)00081-7journal_volume
66pub_type
杂志文章abstract:OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium ha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:Some neuropeptides have direct cardiac effects and also modulate the cardiac effects of catecholamines. Vasopressin is an abundantly available neuropeptide having well known interactions with catecholamines in vascular smooth muscle. The aim of this study was to determine the direct and modulatory effects of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.9.1624
更新日期:1993-09-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN:Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioliga...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.9.764
更新日期:1991-09-01 00:00:00
abstract::The effect of lidocaine on the effective refractory period of the right ventricle (EVRP) was measured in 10 patients using the extra stimulus technique of progressive introduction of premature stimuli until a response could not be elicited. In four patients lidocaine produced a significant decrease in the EVRP, in a f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.5.621
更新日期:1975-09-01 00:00:00
abstract:OBJECTIVE:Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1093/cvr/27.8.1477
更新日期:1993-08-01 00:00:00
abstract::The kinetics of onset of rate-dependent depression of maximum rate of depolarisation (Vmax) of guinea-pig ventricular action potentials were studied for nine Class I anti-arrhythmic drugs using standard microelectrode techniques. The drugs were found to fall into three well-demarcated subgroups with "fast" (lignocaine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.6.344
更新日期:1983-06-01 00:00:00
abstract:OBJECTIVE:This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia. METHODS:Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00132-6
更新日期:1997-08-01 00:00:00
abstract:AIMS:Altered Ca(2+) handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities in protein phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into the local, rather than global, regulation of PP...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu123
更新日期:2014-07-01 00:00:00
abstract::Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentratio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa068
更新日期:2020-07-15 00:00:00
abstract:AIMS:Vascular endothelial growth factors (VEGFs) and their receptors (VEGF-Rs) are among the most powerful factors regulating vascular growth. However, it has remained unknown whether stimulation of VEGF-R1, VEGF-R2 or both of the receptors produces the best angiogenic responses in myocardium. The aim of this study was...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp382
更新日期:2010-04-01 00:00:00
abstract:AIMS:Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy217
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVE:The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. METHODS:After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract:AIMS:The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in pati...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz345
更新日期:2021-01-01 00:00:00
abstract::Integrative genomics studies have greatly advanced our understanding of cardiovascular pathophysiology over the last decade. Here, we highlight the strengths and challenges of this cutting-edge approach and provide examples where novel insights have arisen through the integration of multi-level genomic information and...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs303
更新日期:2013-03-15 00:00:00
abstract::Tension and action potentials have been measured simultaneously from isolated cat papillary muscles. Two groups of experiments are described. In the first group, the external conditions under which the muscle contracted were changed. Specifically, stimulation rate, extra-cellular [Ca++], extracellular [Na++] were alte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.3.210
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVE:Gap junction channels provide for direct electrical coupling between cells, and play an important role in homeostasis and electrical coupling. One of the proteins that form gap junctions, Connexin40 (Cx40), shows restricted expression in the body, and is found in blood vessels and in the atrium and conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00373-9
更新日期:2000-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to compare the temporal sequence and structural relationship between perivascular and interstitial fibrosis and microscopic scarring seen in the left ventricle in response to either a transient or sustained stimulus to fibrosis. DESIGN:In 72 male Wistar rats (250-350 g) the transient stimul...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.741
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS:Patie...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00261-8
更新日期:2000-01-14 00:00:00
abstract::Numerous epidemiological studies documented an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and the extent of atherosclerotic disease. However, clinical interventions targeting HDL cholesterol failed to show clinical benefits with respect to cardiovascular risk reduction, sugge...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu136
更新日期:2014-08-01 00:00:00
abstract:AIMS:A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa205
更新日期:2020-07-16 00:00:00
abstract:AIMS:We have demonstrated an important role of bone marrow-derived stem cells in preservation of myocardial function. We investigated whether Akt-1 of lin(-)c-kit(+) stem cells preserves ventricular function following myocardial infarction (MI). METHODS AND RESULTS:Isolated lin(-)c-kit(+) cells were conjugated with an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq110
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.021
更新日期:2007-11-01 00:00:00
abstract::The effects of both gradual and abrupt coronary occlusion on regional wall function (sonomicrometry) and left ventricular relaxation were studied in the intact dog heart. The ischaemic dysfunction observed in the two interventions as assessed by pressure-length loops showed considerably different patterns. The regiona...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.7.507
更新日期:1987-07-01 00:00:00
abstract:OBJECTIVE:Important physiological and pathophysiological conditions are associated with changes in secretion and synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The aim of this study was to examine the effects of mechanical stretch and endothelin-1 on ANF and BNP secretion and gene exp...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.10.1519
更新日期:1994-10-01 00:00:00
abstract:OBJECTIVE:We have previously demonstrated that nuclear factor kappa B (NFkappaB) activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.025
更新日期:2005-11-01 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:OBJECTIVE:The aim was to clarify the site in the coronary microcirculation that is dilated by an ATP sensitive potassium channel opener, levcromakalim, and to examine whether the magnitude of dilatation is size dependent. METHODS:Coronary arterial microvessels were observed through an intravital microscope equipped wi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.12.1780
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVES:Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17 beta-est...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract:AIMS:Notch signalling is essential for blood vessel formation. During angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of the Notch ligan...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv151
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00144-3
更新日期:1999-09-01 00:00:00