Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: a hypoxia specific mechanism of action.

Abstract:

:Angiostatin is an angiogenesis inhibitor in part generated by and released from platelets. Since platelets upon thrombus formation can give rise to areas of hypoxia, we investigated the effects of angiostatin on endothelial cell migration and apoptosis during hypoxia. Human microvascular endothelial cells (HMVEC-L) were exposed to angiostatin under normoxic or hypoxic conditions. Apoptosis was measured by flow-cytometry. HMVEC-L migration was studied using a modified Boyden Chamber assay, in which migration is MMP-dependent. MMP-2, MMP-14, and VEGF levels were measured using immunoblot, Q-PCR and ELISA. During hypoxia HMVEC-L were protected from angiostatin-induced apoptosis due to increased hypoxia-induced VEGF expression. However, MMP-dependent migration of HMVEC-L was inhibited by angiostatin under hypoxic but not normoxic conditions. Angiostatin decreased MMP-2 at the gene and protein levels only in HMVEC-L exposed to hypoxia. A similar result was obtained for MMP-14. Higher angiostatin concentrations, as would be seen during thrombosis, induced HMVEC-L apoptosis, which was not rescued by VEGF. Under hypoxic conditions angiostatin's primary anti-angiogenic mechanism is likely inhibition of endothelial cell MMP-dependent endothelial cell migration. Only at higher concentrations does angiostatin induce endothelial cell death. This study identifies a novel angiostatin anti-angiogenesis mechanism that is only triggered under pathological-like conditions.

journal_name

Vascul Pharmacol

journal_title

Vascular pharmacology

authors

Radziwon-Balicka A,Ramer C,Moncada de la Rosa C,Zielnik-Drabik B,Jurasz P

doi

10.1016/j.vph.2012.11.003

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

280-91

issue

4

eissn

1537-1891

issn

1879-3649

pii

S1537-1891(12)00200-5

journal_volume

58

pub_type

杂志文章
  • Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.

    abstract::Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injecti...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2017.09.007

    authors: Fioretti AC,Ogihara CA,Cafarchio EM,Venancio DP,de Almeida RL,Antonio BB,Sato MA

    更新日期:2017-12-01 00:00:00

  • Effect of Semecarpus anacardium nut extract on ECM and proteases in mammary carcinoma rats.

    abstract::The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix cons...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2006.12.004

    authors: Mathivadhani P,Shanthi P,Sachdanandam P

    更新日期:2007-06-01 00:00:00

  • β-Adrenoceptors differentially regulate vascular tone and angiogenesis of rat aorta via ERK1/2 and p38.

    abstract::β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2014.04.003

    authors: Perez-Aso M,Flacco N,Carpena N,Montesinos MC,D'Ocon P,Ivorra MD

    更新日期:2014-05-01 00:00:00

  • Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice.

    abstract:OBJECTIVE:Inflammation and oxidative stress play a key role in the initiation, propagation, and development of atherosclerosis. Arterial baroreflex (ABR) dysfunction induced by sinoaortic denervation (SAD) promoted the development of atherosclerosis in ApoE-/- mice. The present work was designed to examine whether ABR ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2016.08.008

    authors: Chen L,Liu DH,Zhang X,Zhang EH,Liu C,Su DF,Cai GJ

    更新日期:2016-12-01 00:00:00

  • PGC-1α ameliorates AngiotensinII-induced eNOS dysfunction in human aortic endothelial cells.

    abstract::Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we i...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2016.05.005

    authors: Li J,Geng XY,Cong XL

    更新日期:2016-08-01 00:00:00

  • Prevention of neointima formation by taurine ingestion after carotid balloon injury.

    abstract::The sulfur-containing amino acid, taurine, has been shown to ameliorate the vascular disorders. We examined the effects of taurine ingestion on intimal thickening following balloon injury. Balloon injury was induced in the left common carotid artery of Wistar rats. Taurine (3% (w/v)) was mixed in the drinking water fr...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2010.07.003

    authors: Murakami S,Sakurai T,Toda Y,Morito A,Sakono M,Fukuda N

    更新日期:2010-09-01 00:00:00

  • Bemiparin, an effective and safe low molecular weight heparin: a review.

    abstract::Bemiparin is a low molecular weight heparin (LMWH) indicated for the acute treatment of deep vein thrombosis with or without pulmonary embolism, for the prophylaxis of venous thromboembolism in surgical and non-surgical patients and for the prevention of clotting in the extracorporeal circuit during hemodialysis. Due ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.vph.2014.03.001

    authors: Ciccone MM,Cortese F,Corbo F,Corrales NE,Al-Momen AK,Silva A,Zito A,Pinto M,Gesualdo M,Scicchitano P

    更新日期:2014-07-01 00:00:00

  • Optogenetic approach for functional assays of the cardiovascular system by light activation of the vascular smooth muscle.

    abstract::Cardiovascular diseases are the major challenge to modern medicine. Intervention to cardiovascular cells is crucial for treatment of the diseases. Here we report a novel intervention to vascular smooth muscle (VSM) cells by optogenetics. Channelrhodopsin in a tandem with YFP was selectively expressed in smooth muscle ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2015.03.006

    authors: Wu Y,Li SS,Jin X,Cui N,Zhang S,Jiang C

    更新日期:2015-08-01 00:00:00

  • Modulation of the monocyte/macrophage system in heart failure by targeting heme oxygenase-1.

    abstract::Upon myocardial infarction (MI) immune system becomes activated by extensive necrosis of cardiomyocytes releasing intracellular molecules called damage-associated molecular patterns. Overactive and prolonged immune responses are likely to be responsible for heart failure development and progression in patients survivi...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.vph.2018.08.011

    authors: Tomczyk M,Kraszewska I,Dulak J,Jazwa-Kusior A

    更新日期:2019-01-01 00:00:00

  • Interaction between bone morphogenetic proteins and endothelin-1 in human pulmonary artery smooth muscle.

    abstract::Genetic mutations in bone morphogenetic protein receptor 2 (BMPR2) have been shown to occur in patients with familial and idiopathic pulmonary arterial hypertension (PAH). However the interactions between ligands for this receptor and other mediators implicated in heritable PAH have not been investigated. This study e...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2009.09.001

    authors: Din S,Sarathchandra P,Yacoub MH,Chester AH

    更新日期:2009-11-01 00:00:00

  • Sildenafil reduces aortic endothelial dysfunction and structural damage in spontaneously hypertensive rats: Role of NO, NADPH and COX-1 pathways.

    abstract::Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endoth...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2019.106601

    authors: Leal MAS,Aires R,Pandolfi T,Marques VB,Campagnaro BP,Pereira TMC,Meyrelles SS,Campos-Toimil M,Vasquez EC

    更新日期:2020-01-01 00:00:00

  • Endothelial dysfunction in young healthy men is associated with aspirin resistance.

    abstract::The aim of this study was to investigate the relation between endothelial dysfunction and aspirin response in a young healthy population (102 men aged 18-40). Initial concentrations of the NO pathway metabolites (ADMA, l-arginine, SDMA), cardiovascular risk markers, oxidative stress markers (MDA, thiol index), sICAM1,...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2015.02.001

    authors: Doroszko A,Szahidewicz-Krupska E,Janus A,Jakubowski M,Turek A,Ilnicka P,Szuba A,Mazur G,Derkacz A

    更新日期:2015-04-01 00:00:00

  • Blood pressure variability provokes vascular β-adrenoceptor desensitization in rats.

    abstract::Spontaneous variation in blood pressure is defined as 'blood pressure variability' (BPV). Sinoaortic denervation (SAD) is characterized by BPV without sustained hypertension. In the present study, we investigated whether BPV could be related to vascular β-adrenoceptor desensitization in rats. Three days after surgery ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2016.05.007

    authors: Rocha ML,Silva BR,Lunardi CN,Ramalho LN,Bendhack LM

    更新日期:2016-07-01 00:00:00

  • Neurokinin3 receptor regulation of the airways.

    abstract::Neurokinin(3) (NK(3)) receptors may regulate the airways primarily through actions on the nerves. In the periphery, airway parasympathetic ganglia neurons are depolarized following NK(3) receptor activation resulting subsequently in the facilitation of synaptic transmission. Such an effect may account for the excessiv...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.vph.2005.08.031

    authors: Canning BJ

    更新日期:2006-10-01 00:00:00

  • Antithrombotic effect of the type III collagen-related octapeptide (KOGEOGPK) in the mouse.

    abstract::Platelet adhesion to subendothelial types I and III collagens exposed upon vascular injury plays a crucial role in hemostasis and thrombosis. We previously identified a KOGEOGPK sequence (O for hydroxyproline) within type III collagen interacting with platelets, and demonstrated a strong inhibitory effect of the KOGEO...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2005.09.006

    authors: Maurice P,Pires V,Amant C,Kauskot A,Da Nascimento S,Sonnet P,Rochette J,Legrand C,Fauvel-Lafeve F,Bonnefoy A

    更新日期:2006-01-01 00:00:00

  • Propranolol-induced relaxation in the rat basilar artery.

    abstract::Propranolol is a non-selective beta-adrenergic receptor blocker used in the treatment of cardiovascular diseases and migraine prophylaxis. Although it has been shown that propranolol dilates the peripheral arteries of rat, its action in the central nervous system vasculature has not been investigated. In this study, t...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2012.12.004

    authors: Cekic EG,Soydan G,Guler S,Babaoglu MO,Tuncer M

    更新日期:2013-04-01 00:00:00

  • The Fra-2 transgenic mouse model of systemic sclerosis.

    abstract::In systemic sclerosis, microvascular injury often precedes the development of fibrosis. Whereas the development of digital ulcers and skin fibrosis causes high morbidity, the affection of internal organs, in particular complications such as interstitial lung disease and pulmonary (arterial) hypertension, account for t...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.vph.2012.12.001

    authors: Maurer B,Distler JH,Distler O

    更新日期:2013-03-01 00:00:00

  • Possible involvement of enhanced arginase activity due to up-regulated arginases and decreased hydroxyarginine in accelerating intimal hyperplasia with hyperglycemia.

    abstract::The present study was designed to investigate the roles of enhanced arginase activity due to up-regulated arginases and the decreased hydroxyarginine for accelerating intimal hyperplasia with hyperglycemia. Thirteen weeks after injection of alloxan or physiological saline, endothelial denudation of the carotid artery ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2007.08.001

    authors: Ishizaka M,Nagai A,Iwanaga M,Imamura M,Azuma H

    更新日期:2007-11-01 00:00:00

  • Effects of 17 β-estradiol on lipopolysacharride-induced intracellular adhesion molecule-1 mRNA expression and Ca²+ homeostasis alteration in human endothelial cells.

    abstract::Recent evidence showed that 17 β-estradiol (E₂) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca²+ concentration ([Ca²+](i)) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E₂ (1 μM, 24 h) on the expression of intracellul...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2010.09.001

    authors: Thor D,Zhang R,Anderson L,Bose DD,Dubé GP,Rahimian R

    更新日期:2010-11-01 00:00:00

  • Vasodilatation produced by fasudil mesylate in vivo and in vitro.

    abstract::To investigate the vasorelaxant effect of fasudil mesylate (FM) in vivo and in vitro. The relaxation effect of FM was studied using cerebral vasospasm (CVS) model in vivo and isolated aortic rings in vitro. FM (0.35, 1.2, 3.5 mg·kg⁻¹) increased cerebrovascular flow (CVF) and femoral blood flow (FBF) dose-dependently i...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2011.06.005

    authors: Li Q,Chen Y,Sun L,Fu G,Guo L

    更新日期:2011-11-01 00:00:00

  • Ozagrel a thromboxane A2 synthase inhibitor extenuates endothelial dysfunction, oxidative stress and neuroinflammation in rat model of bilateral common carotid artery occlusion induced vascular dementia.

    abstract::The present study investigates the potential of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water maze (MWM) test was employed on 7th day p...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2020.106827

    authors: Bhatia P,Kaur G,Singh N

    更新日期:2020-12-17 00:00:00

  • Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels.

    abstract::In this study, we have investigated the actions of danshensu, an active, water-extractable component of the medicinal herb danshen (Salvia miltiorrhiza), on rat isolated coronary artery rings precontracted with 1 microM 5-hydroxytryptamine (5-HT) and its action compared to the water-extractable fraction of the herb. E...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2006.10.011

    authors: Lam FF,Yeung JH,Chan KM,Or PM

    更新日期:2007-04-01 00:00:00

  • Adrenoceptor and cholinoceptor modulation of rat pulmonary vein cardiac muscle contractility.

    abstract::Cardiac muscle extends into mammalian pulmonary veins for variable distances according to species. This study has addressed the autonomic control of electrically paced cardiac muscle of the pulmonary vein of the rat. Contractile responses of Wistar rat pulmonary veins were investigated under isometric conditions in vi...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2006.09.005

    authors: Sweeney CM,Jones JF,Bund SJ

    更新日期:2007-03-01 00:00:00

  • Antiretroviral drug-induced endothelial dysfunction is improved by dual PPARα/γ stimulation in obesity.

    abstract::Obesity rates are rising in HIV-infected populations; however, the putative role of highly active antiretroviral therapy (HAART) in the development of endothelial and cardiovascular derangements in the presence of pre-existing overweight/obesity is unclear. Although dual peroxisome proliferator-activated receptors-alp...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2019.106577

    authors: Kamau F,Strijdom H,Mwangi P,Blackhurst D,Imperial E,Salie R

    更新日期:2019-10-01 00:00:00

  • Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

    abstract:BACKGROUND:Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only f...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2015.10.006

    authors: Barbieri L,Pergolini P,Verdoia M,Rolla R,Nardin M,Marino P,Bellomo G,Suryapranata H,De Luca G,Novara Atherosclerosis Study Group (NAS).

    更新日期:2016-04-01 00:00:00

  • Emodin upregulates urokinase plasminogen activator, plasminogen activator inhibitor-1 and promotes wound healing in human fibroblasts.

    abstract::Urokinase plasminogen activator (uPA) system is important for several biological processes that call for extracellular proteolysis, fibrinolysis, cell migration, proliferation and angiogenesis. The current study highlights the fibrinolytic and wound healing potential of emodin, an anthraquinone, with relevance to the ...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2008.02.002

    authors: Radha KS,Madhyastha HK,Nakajima Y,Omura S,Maruyama M

    更新日期:2008-04-01 00:00:00

  • Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells.

    abstract:BACKGROUND:Tissue Factor (TF) plays a pivotal role in coronary thrombosis. Oxidized low-density lipoproteins (oxLDL) are crucial in development of atherosclerosclerosis. Moreover, oxLDL are known to induce TF expression on several cell types including endothelial cells. The lectin-type oxidized LDL receptor 1 (LOX-1) r...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2020.106822

    authors: Cimmino G,Conte S,Morello A,Pellegrino G,Marra L,Calì G,Golino P,Cirillo P

    更新日期:2020-11-21 00:00:00

  • Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide.

    abstract::Since the discovery of the importance of nitric oxide (NO) to the human body three decades ago, numerous laboratory and clinical studies have been done to explore its potential therapeutic actions on many organs. In the cardiovascular system, NO works as a volatile signaling molecule regulating the vascular permeabili...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.vph.2014.08.001

    authors: Ma S,Ma CC

    更新日期:2014-11-01 00:00:00

  • The influence of sulindac on diabetic cardiomyopathy: a non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats.

    abstract::The aim of the present study was to investigate the cardioprotective activity of sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats. Echocardiogr...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2005.02.012

    authors: Krishna KM,Gopal GS,Chalam CR,Madan K,Kumar VK,Prakash GJ,Annapurna A

    更新日期:2005-08-01 00:00:00

  • Cardioprotective effect of resvaratrol pretreatment on myocardial ischemia-reperfusion induced injury in rats.

    abstract:OBJECTIVE:The major objective of the present study was to examine the cardioprotective effect of resveratrol, an antioxidant presents in red wine, in the rat after ischemia-reperfusion (I/R). DESIGN:The left coronary artery was in occlusion for 30 min followed by a 120 min reperfusion in anesthetized rats. Animals wer...

    journal_title:Vascular pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.vph.2006.04.002

    authors: Shen M,Jia GL,Wang YM,Ma H

    更新日期:2006-08-01 00:00:00