Abstract:
:Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization, as evaluated by angiography, is weak. In this study, we report an angiogenesis-independent effect of VEGF on ischemic skeletal muscle, ie, upregulation of myoglobin after VEGF treatment. Mice received intramuscular injection with adenoviral VEGF-A or either adenoviral LacZ or PBS as control, followed by surgical induction of acute hindlimb ischemia at day 3. At day 6, capillary density was increased in calf muscle of Ad.VEGF-treated versus control mice (P<0.01). However, angiographic score of collateral arteries was unchanged between Ad.VEGF-treated and control mice. More interestingly, an increase in myoglobin was observed in Ad.VEGF-treated mice. Active myoglobin was 1.5-fold increased in calf muscle of Ad.VEGF-treated mice (P< or =0.01). In addition, the number of myoglobin-stained myofibers was 2.6-fold increased in Ad.VEGF-treated mice (P=0.001). Furthermore, in ischemic muscle of 15 limb amputation patients, VEGF and myoglobin were coexpressed. Finally, in cultured C2C12 myotubes treated with rhVEGF, myoglobin mRNA was 2.8-fold raised as compared with PBS-treated cells (P=0.02). This effect could be blocked with the VEGF receptor tyrosine kinase inhibitor SU5416. In conclusion, we show that VEGF upregulates myoglobin in ischemic muscle both in vitro and in vivo. Increased myoglobin expression in VEGF-treated muscle implies an improved muscle oxygenation, which may, at least partly, explain observed clinical improvements in VEGF-treated patients, in the absence of improved vascularization.
journal_name
Circ Resjournal_title
Circulation researchauthors
van Weel V,Deckers MM,Grimbergen JM,van Leuven KJ,Lardenoye JH,Schlingemann RO,van Nieuw Amerongen GP,van Bockel JH,van Hinsbergh VW,Quax PHdoi
10.1161/01.RES.0000133247.69803.c3subject
Has Abstractpub_date
2004-07-09 00:00:00pages
58-66issue
1eissn
0009-7330issn
1524-4571pii
01.RES.0000133247.69803.c3journal_volume
95pub_type
杂志文章abstract:RATIONALE:Activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. OBJECTIVE:To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K(...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.266445
更新日期:2012-08-03 00:00:00
abstract::The objectives of this study were to measure action potential parameters in enzyme-dissociated, adult rat ventricular myocytes stimulated at 1 Hz, to compare these measurements with those obtained from intact ventricular tissue, and to determine myocyte and tissue responses at stimulus frequencies between 0.1 and 5 Hz...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.3.280
更新日期:1983-03-01 00:00:00
abstract::To elucidate the local effects of renin in the coronary circulation, we examined local angiotensin (Ang) I and II formation, as well as coronary vasoconstriction in response to renin administration, and compared the effects with exogenous infused Ang I. We perfused isolated hearts from rats overexpressing the human an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.1.13
更新日期:1998-01-09 00:00:00
abstract:RATIONALE:Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein that is expressed in mammalian myocardium under normal conditions and upregulated in pathological states such as heart failure. UCP2 is thought to protect cardiomyocytes against oxidative stress by dissipating the mitochondrial proton gradien...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206631
更新日期:2010-03-05 00:00:00
abstract::The mechanism of adenosine-induced inhibition of Ca2+ currents was studied by recording single-channel Ca2+ currents from cell-attached patches on isolated guinea pig ventricular cells with pipettes containing 50 or 100 mM Ba2+. Numerous 100-msec depolarization steps were applied repetitively at 2 Hz from the resting ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1134
更新日期:1990-11-01 00:00:00
abstract::To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 month...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.536
更新日期:1996-04-01 00:00:00
abstract::Cation channels activated by Ca(2+) store depletion have been proposed to mediate Ca(2+) influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a functional role in pulmonary artery smooth muscle cells (PASMCs). In intact rat pulmonary artery rings, cyclopiazonic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2201.100315
更新日期:2001-11-09 00:00:00
abstract::The remodeling of ventricular gap junctions, as defined by changes in size, distribution, or function, is a prominent feature of diseased myocardium. However, the regulation of assembly and maintenance of gap junctions remains poorly understood. To investigate N-cadherin function in the adult myocardium, we used a flo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000181132.11393.18
更新日期:2005-09-02 00:00:00
abstract:RATIONALE:Mammalian cardiomyocytes withdraw from the cell cycle during early postnatal development, which significantly limits the capacity of the adult mammalian heart to regenerate after injury. The regulatory mechanisms that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.248880
更新日期:2011-09-02 00:00:00
abstract::The aim of the study was to investigate whether the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in the adrenal gland and to explore the mechanisms of this action. Twelve-week-old male Sprague-Dawley rats were studied: 22 rats were maintained on a regul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.857
更新日期:1997-11-01 00:00:00
abstract::In 36 normolipemic pigs randomized to a 4-week feeding with regular pig chow (n = 18, control group) or chow supplemented with cod liver oil (1 ml/kg per day) (n = 18, treated group), treatment with cod liver oil produced a significant decrease in serum cholesterol, low density lipoprotein cholesterol, and triglycerid...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.4.769
更新日期:1992-10-01 00:00:00
abstract::The predominant cardiac Ca2+/calmodulin-dependent protein kinase (CaMK) is CaMKIIdelta. Here we acutely overexpress CaMKIIdeltaC using adenovirus-mediated gene transfer in adult rabbit ventricular myocytes. This circumvents confounding adaptive effects in CaMKIIdeltaC transgenic mice. CaMKIIdeltaC protein expression a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000200739.90811.9f
更新日期:2006-02-03 00:00:00
abstract:RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biolo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302476
更新日期:2014-04-25 00:00:00
abstract::In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.1.57
更新日期:1983-01-01 00:00:00
abstract::We used plethysmograph techniques to measure or calculate the tissue and capillary forces and flows (capillary pressure, tissue and plasma oncotic pressure, transcapillary pressure drop, lymph flow, and interstitial pressure) in a dog hindpaw preparation in situ at three different venous pressures (PV). Since lymph wa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.2.245
更新日期:1976-08-01 00:00:00
abstract:RATIONALE:Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Further...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306723
更新日期:2015-09-11 00:00:00
abstract::Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.2.293
更新日期:1978-08-01 00:00:00
abstract::The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In gui...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.5.e49
更新日期:2001-03-16 00:00:00
abstract:RATIONALE:Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs) may confer vascular hom...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311450
更新日期:2017-12-08 00:00:00
abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.6.759
更新日期:1979-06-01 00:00:00
abstract::14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000104084.88317.91
更新日期:2003-11-28 00:00:00
abstract:RATIONALE:Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE:To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS:We studied 538 CHD trios using genome-wide dense single nucle...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.115.304458
更新日期:2014-10-24 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::This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Six...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.6.1020
更新日期:1988-12-01 00:00:00
abstract::Ventricular arrhythmias that accompany myocardial infarction in dogs may be secondary to the altered electrophysiological properties of the subendocardial Purkinje fibers that survive 24 hours after the coronary occlusion. To better understand the ionic mechanisms that underlie the altered electrical activity of these...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.955
更新日期:1989-10-01 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:RATIONALE:Mechanical stress plays an important role in proliferation of venous smooth muscle cells (SMCs) in neointima, a process of formation that contributes to failure of vein grafts. However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs. OBJECTIVE:The objective of this study...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.222588
更新日期:2010-11-12 00:00:00
abstract::Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000264081.78659.45
更新日期:2007-04-13 00:00:00
abstract::Morphometric data from stable (nonedematous) isolated dog lungs, perfused with nearly cell-free perfusates, were compared to similar stereological evaluations of isolated dog lungs after induction of severe acute hydrostatic edema. In the edematous lungs, capillary surface and volume densities were substantially incre...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.1.72
更新日期:1978-07-01 00:00:00
abstract::Patients with diabetes mellitus have >2× the risk for developing heart failure (HF; HF with reduced ejection fraction and HF with preserved ejection fraction). Cardiovascular outcomes, hospitalization, and prognosis are worse for patients with diabetes mellitus relative to those without. Beyond the structural and func...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311371
更新日期:2019-01-04 00:00:00