Abstract：
BACKGROUND AND PURPOSE:Bleomycin (BLM), one of the most common sclerosants, is often used to treat venous malformations (VMs). The present study was designed to investigate whether endothelial mesenchymal transition (EndoMT) contributes to the therapeutic effects of BLM. EXPERIMENTAL APPROACH:Endothelial and mesenchymal markers of HUVECs were measured by immunofluorescence, real-time quantitative PCR and Western blot analysis. Cell migration and tube formation assays were performed to evaluate endothelial cell function. Slug small-interfering RNA and specific inhibitors [Z-VAD-FMK for pan caspases, rapamycin for mammalian target of rapamycin (mTOR)] were used to investigate the mechanism. KEY RESULTS:Long term (48 h or longer) treatment with BLM (0.1 mU·mL(-1) ) induced EndoMT in HUVECs, as manifested by a reduction in the expression of vascular endothelial-cadherin and an up-regulation in the expression of α-smooth muscle actin and fibroblast specific protein-1, as well as activation of the transcription factor Slug. The size and protein content of the transformed cells were increased. BLM also enhanced the migration of HUVECs but diminished their tube formation. By employing rapamycin, we demonstrated that activation of the mTOR pathway is involved in BLM-induced EndoMT in HUVECs. CONCLUSIONS AND IMPLICATIONS:Our results show that a Slug-dependent EndoMT process is involved in BLM-induced therapeutic effects on endothelial cells and, more importantly, indicate the potential role of this process in the sclerotherapy of VMs.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Zhang W,Chen G,Ren JG,Zhao YFdoi
10.1111/bph.12355subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1210-20issue
6eissn
0007-1188issn
1476-5381journal_volume
170pub_type
杂志文章abstract：:The distribution of beta-adrenoceptor subtypes in slide-mounted sections of guinea-pig kidney has been examined by the technique of in vitro labelling combined with autoradiography. Binding of (-)-[125I]-cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08867.x
更新日期：1985-06-01 00:00:00
abstract：:1 The fate of (15S)-15-methyl prostaglandin E(2) methyl ester and 16,16-dimethyl prostaglandin E(2) in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E(2) by means of bioassay.2 Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08456.x
更新日期：1978-02-01 00:00:00
abstract：:1. A study has been made of serum, mixed and parotid salivary levels attained in normal volunteers following oral dosage of 500 mg phenoxymethylpenicillin tablets, 500 mg crushed phenoxymethylpenicillin tablets in capsules, 500 mg ampicillin, 500 mg cloxacillin and 500 mg cephalexin.2. High mixed saliva levels were ob...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07173.x
更新日期：1971-09-01 00:00:00
abstract：:1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12754.x
更新日期：1992-10-01 00:00:00
abstract：:1. Experiments were performed with peptidase inhibitors on rabbit aortic strip preparations, to determine whether endogenous peptidase activity can influence the potency estimates for angiotensin receptor agonists and antagonists in this tissue. 2. Angiotensin II (A II) and angiotensin III (A III) both induced concent...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14310.x
更新日期：1992-05-01 00:00:00
abstract：:1. Lowering of the extracellular Mg(2+)-concentration induces various patterns of epileptiform activity in combined rat entorhinal cortex-hippocampal brain slices. After a prolonged period of exposure to Mg(2+)-free medium seizure-like events in the entorhinal cortex change to a state of late recurrent discharges whic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15710.x
更新日期：1996-10-01 00:00:00
abstract：:The pharmaceutical industry is testing new potential drugs for their propensity to prolong human cardiac repolarization, and regards this as a sign of proarrhythmic risk. Many studies have dethroned the common perception that prolonged repolarization is a reliable surrogate marker for torsades de pointes (TdP) arrhyth...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0707299
更新日期：2007-08-01 00:00:00
abstract：:781094 (2-(2(1, 4-benzodioxanyl))-2-imidazoline hydrochloride) is a potent competitive inhibitor of the aggregatory responses of human platelets induced by adrenaline (pA2 = 7.3) and UK-14304. 781094 is a more potent inhibitor of the pro-aggregatory response to clonidine than of that to methoxamine. The alpha 2/alpha ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb11012.x
更新日期：1983-06-01 00:00:00
abstract：:1. We previously demonstrated that cyclopiazonic acid (CPA), an inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum, induced rhythmic relaxations of active tension in the endothelium-denuded small arteries of the mesentery and the ear of the rabbit, but that this agent failed to induce rhythmic responses in the e...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15392.x
更新日期：1996-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707605
更新日期：2008-02-01 00:00:00
abstract：:1. The presence of an endogenous digitalis-like factor (EDLF) in the plasma of both normal and volume expanded animals is well documented. In this study we have used ouabain and bufalin as pharmacological analogues to mimic the renal effects of EDLF and to investigate whether any interaction occurs between atrial natr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12852.x
更新日期：1993-03-01 00:00:00
abstract：:1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of pirace...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15218.x
更新日期：1996-02-01 00:00:00
abstract：:1. The relative proportions of beta 1- and beta 2-adrenoceptors were determined by radioligand binding studies in three different rat myocardial preparations: membranes prepared from rat ventricle (ventricular membranes), membranes prepared from rat isolated ventricular myocytes (myocyte membranes), and myocytes isola...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16384.x
更新日期：1995-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with coronary artery disease. We tested the hypothesis that a reduction of resting heart rate with the cardiac pacemaker I(f) current inhibitor ivabradine prevents the endot...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.116
更新日期：2008-06-01 00:00:00
abstract：:1. Inositol phospholipid hydrolysis was examined in human cerebral cortex slices by a [3H]-inositol prelabelling assay. 2. Enhancement of [3H]-inositol phosphates accumulation was observed in the presence of carbachol, noradrenaline, histamine, 5-hydroxytryptamine (5-HT) and depolarizing concentrations of KCl. 3. Desp...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12048.x
更新日期：1990-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.8
更新日期：2008-04-01 00:00:00
abstract：:1. The effects of acetylcholine (ACh) on membrane potential, relaxation and cyclic GMP levels were compared to the NO donor L-nitrosocysteine (Cys-NO) in segments of guinea-pig coronary artery. 2. ACh and Cys-NO produced concentration-dependent relaxations of muscles contracted with the H1 receptor agonist, 2-(2-amino...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14851.x
更新日期：1994-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behaviour in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly elucidated. Thus, we in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14423
更新日期：2018-09-01 00:00:00
abstract：:1 A study was made of desensitization in chronically denervated and in normally innervated mouse soleus muscles. 2 Very high concentrations of acetylcholine produced small contractions of the innervated muscles; these were reduced in size when the addition was repeated 1 min after wash-out. 3 Desensitization in innerv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07620.x
更新日期：1975-09-01 00:00:00
abstract：:1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09011.x
更新日期：1992-03-01 00:00:00
abstract：:1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08684.x
更新日期：1979-11-01 00:00:00
abstract：:1. The aim of this study was to investigate the cardiovascular effects of a novel, potent and specific phosphodiesterase 5 (PDE 5) inhibitor, 1,3 dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl)-pyrazolo[3,4-d]pyrimidin-4-(5H)-one (DMPPO) in phenylephrine-precontracted rat aortic rings and different in vivo rat p...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15548.x
更新日期：1996-07-01 00:00:00
abstract：:1. Inhibition of nitric oxide generation with Nw-nitro-L-arginine (nitroarginine) reduced vasodilator responses to bradykinin and acetylcholine and enhanced those to nitroprusside in the rat isolated perfused kidney, preconstricted with phenylephrine. 2. Inhibition of cyclo-oxygenase with indomethacin, decreased the v...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14513.x
更新日期：1992-11-01 00:00:00
abstract：:1. Recent studies demonstrated that the cardiac calpain system is activated during ischaemic events and is involved in cardiomyocyte injury. The aim of this study was to investigate the contribution of AT(1) and AT(2) receptors in the regulation of calpain-mediated myocardial damage following myocardial infarction (MI...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703860
更新日期：2001-02-01 00:00:00
abstract：:1 Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow. 2 Metiamide, in doses which inhibited pentagastrin-stimulated acid secretion, produced no increase in gastric ac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07361.x
更新日期：1975-02-01 00:00:00
abstract：:Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10766.x
更新日期：1984-06-01 00:00:00
abstract：:PPARδ is a ligand-activated receptor that dimerizes with another nuclear receptor of the retinoic acid receptor family. The dimers interact with other co-activator proteins and form active complexes that bind to PPAR response elements and promote transcription of genes involved in lipid metabolism. It appears that var...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12950
更新日期：2015-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate wh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14802
更新日期：2019-10-01 00:00:00
abstract：:The effects of 15-hydroperoxy metabolites of arachidonic acid on vascular tone were evaluated in the perfused mesenteric preparation, the isolated perfused lung and segments of pulmonary arteries of the rat. In the mesenteric preparation, precontracted with phenylephrine, both 15-hydroperoxy-5,8,11,13-eicosatetraenoic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11256.x
更新日期：1987-07-01 00:00:00
abstract：:1. Perivascular nerves of the sheep middle cerebral artery show immunoreactivity for both vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). 2. Rings of endothelium-denuded sheep middle cerebral artery precontracted with 5-hydroxytryptamine were relaxed by CGRP (maximum relaxation = 87...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12213.x
更新日期：1991-03-01 00:00:00
