Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1.

Abstract:

:Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and vascular cells to hypoxia or AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, modulates the expression of genes encoding the angiogenic factors angiopoietin-1 (ANGPT1), ANGPT2, placental growth factor, and platelet-derived growth factor-B. Loss-of-function effects were also observed in HIF-1alpha-null embryonic stem cells. Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5. In all cases, there was complete concordance between the effects of hypoxia and AdCA5. Injection of AdCA5 into mouse eyes induced neovascularization in multiple capillary beds, including those not responsive to VEGF alone. Analysis of gene expression revealed increased expression of ANGPT1, ANGPT2, platelet-derived growth factor-B, placental growth factor, and VEGF mRNA in AdCA5-injected eyes. These results indicate that HIF-1 functions as a master regulator of angiogenesis by controlling the expression of multiple angiogenic growth factors and that adenovirus-mediated expression of a constitutively active form of HIF-1alpha is sufficient to induce angiogenesis in nonischemic tissue of an adult animal.

journal_name

Circ Res

journal_title

Circulation research

authors

Kelly BD,Hackett SF,Hirota K,Oshima Y,Cai Z,Berg-Dixon S,Rowan A,Yan Z,Campochiaro PA,Semenza GL

doi

10.1161/01.RES.0000102937.50486.1B

subject

Has Abstract

pub_date

2003-11-28 00:00:00

pages

1074-81

issue

11

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000102937.50486.1B

journal_volume

93

pub_type

杂志文章
  • Cadherins, RhoA, and Rac1 are differentially required for stretch-mediated proliferation in endothelial versus smooth muscle cells.

    abstract::Abnormal mechanical forces can trigger aberrant proliferation of endothelial and smooth muscle cells, as observed in the progression of vascular diseases such as atherosclerosis. It has been previously shown that cells can sense physical forces such as stretch through adhesions to the extracellular matrix. Here, we se...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.107.158329

    authors: Liu WF,Nelson CM,Tan JL,Chen CS

    更新日期:2007-08-31 00:00:00

  • Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein- and fibroblast growth factor-signaling pathways.

    abstract:RATIONALE:The epicardium contributes to the majority of nonmyocardial cells in the adult heart. Recent studies have reported that the epicardium is derived from Nkx2.5-positive progenitors and can differentiate into cardiomyocytes. Not much is known about the relation between the myocardial and epicardial lineage durin...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.203083

    authors: van Wijk B,van den Berg G,Abu-Issa R,Barnett P,van der Velden S,Schmidt M,Ruijter JM,Kirby ML,Moorman AF,van den Hoff MJ

    更新日期:2009-08-28 00:00:00

  • Nonlinear dynamics of rate-dependent activation in models of single cardiac cells.

    abstract::Recent studies in isolated cardiac tissue preparations have demonstrated the applicability of a one-dimensional difference equation model describing the global behavior of a driven nonpacemaker cell to the understanding of rate-dependent cardiac excitation. As a first approximation to providing an ionic basis to compl...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.6.1510

    authors: Vinet A,Chialvo DR,Michaels DC,Jalife J

    更新日期:1990-12-01 00:00:00

  • Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes.

    abstract::Atrial tissue expresses both connexin 40 (Cx40) and 43 (Cx43) proteins. To assess the relative roles of Cx40 and Cx43 in atrial electrical propagation, we synthesized cultured strands of atrial myocytes derived from mice with genetic deficiency in Cx40 or Cx43 expression and measured propagation velocity (PV) by high-...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000250607.34498.b4

    authors: Beauchamp P,Yamada KA,Baertschi AJ,Green K,Kanter EM,Saffitz JE,Kléber AG

    更新日期:2006-11-24 00:00:00

  • Voltage-dependent Ca2+ channels in resistance arteries from spontaneously hypertensive rats.

    abstract::Alterations in voltage-dependent Ca2+ channels in the arterial smooth muscle cells of spontaneously hypertensive rats (SHR) were investigated using the whole-cell voltage clamp and compared with Wistar-Kyoto (WKY) rats. Single cells were freshly isolated from resistance mesenteric arteries from 4- to 5-week-old (young...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.6.1090

    authors: Ohya Y,Abe I,Fujii K,Takata Y,Fujishima M

    更新日期:1993-12-01 00:00:00

  • Normal levels of fibrinopeptide A in patients with primary hyperlipidemia.

    abstract::Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.45.3.347

    authors: Nossel HL,Smith FR,Seplowitz AH,Dell RB,Sciacca RR,Merskey C,Goodman DS

    更新日期:1979-09-01 00:00:00

  • Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition, and heart protection from ischemic injury.

    abstract::The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted kno...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000134921.50377.61

    authors: Hilfiker-Kleiner D,Hilfiker A,Fuchs M,Kaminski K,Schaefer A,Schieffer B,Hillmer A,Schmiedl A,Ding Z,Podewski E,Podewski E,Poli V,Schneider MD,Schulz R,Park JK,Wollert KC,Drexler H

    更新日期:2004-07-23 00:00:00

  • Thrombin stimulates smooth muscle cell differentiation from peripheral blood mononuclear cells via protease-activated receptor-1, RhoA, and myocardin.

    abstract:RATIONALE:Smooth muscle precursor cells have previously been reported to reside in bone marrow and in the circulation, but little is currently known regarding the proximate stimuli for smooth muscle cell differentiation of these putative progenitors. OBJECTIVE:Because local thrombin generation occurs as an initial res...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.199984

    authors: Martin K,Weiss S,Metharom P,Schmeckpeper J,Hynes B,O'Sullivan J,Caplice N

    更新日期:2009-07-31 00:00:00

  • Effect of in vitro organic nitrate tolerance on relaxation, cyclic GMP accumulation, and guanylate cyclase activation by glyceryl trinitrate and the enantiomers of isoidide dinitrate.

    abstract::Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.4.693

    authors: Bennett BM,Schröder H,Hayward LD,Waldman SA,Murad F

    更新日期:1988-10-01 00:00:00

  • Beta-adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway.

    abstract::Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hour...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000054624.03539.b4

    authors: Remondino A,Kwon SH,Communal C,Pimentel DR,Sawyer DB,Singh K,Colucci WS

    更新日期:2003-02-07 00:00:00

  • In vivo estimation of cardiac transmembrane current.

    abstract::The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in viv...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.2.424

    authors: Witkowski FX,Kavanagh KM,Penkoske PA,Plonsey R

    更新日期:1993-02-01 00:00:00

  • Variation in the velocity, deformation, and adhesion energy density of leukocytes rolling within venules.

    abstract::Leukocyte rolling along the endothelium in inflammation is caused by continuous formation and breakage of bonds between selectin adhesion molecules and their ligands. We investigated trauma-induced leukocyte rolling in venules (diameter, 23 to 58 microns; wall shear stress, 1.2 to 35 dyne/cm2) of the exteriorized rat ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.79.6.1122

    authors: Damiano ER,Westheider J,Tözeren A,Ley K

    更新日期:1996-12-01 00:00:00

  • Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration.

    abstract::Smooth muscle cell migration in response to platelet-derived growth factor (PDGF) is a key event in several vascular pathologies, including atherosclerosis and restenosis. PDGF increases intracellular levels of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs), but the ROS sensitivity of migration ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000126848.54740.4A

    authors: Weber DS,Taniyama Y,Rocic P,Seshiah PN,Dechert MA,Gerthoffer WT,Griendling KK

    更新日期:2004-05-14 00:00:00

  • Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death.

    abstract::Remodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remod...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000261352.81736.37

    authors: Keogh RJ,Harris LK,Freeman A,Baker PN,Aplin JD,Whitley GS,Cartwright JE

    更新日期:2007-03-30 00:00:00

  • Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo.

    abstract::Hemodynamics play an important role in cardiovascular development, and changes in blood flow can cause congenital heart malformations. The endothelium and endocardium are subjected to mechanical forces, of which fluid shear stress is correlated to blood flow velocity. The shear stress responsive genes lung Krüppel-lik...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000171901.40952.0d

    authors: Groenendijk BC,Hierck BP,Vrolijk J,Baiker M,Pourquie MJ,Gittenberger-de Groot AC,Poelmann RE

    更新日期:2005-06-24 00:00:00

  • A novel mouse model of atherosclerotic plaque instability for drug testing and mechanistic/therapeutic discoveries using gene and microRNA expression profiling.

    abstract:RATIONALE:The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans. OBJECTIVE:Development and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.113.301562

    authors: Chen YC,Bui AV,Diesch J,Manasseh R,Hausding C,Rivera J,Haviv I,Agrotis A,Htun NM,Jowett J,Hagemeyer CE,Hannan RD,Bobik A,Peter K

    更新日期:2013-07-19 00:00:00

  • Diverse origin and function of cells with endothelial phenotype obtained from adult human blood.

    abstract::Cells with endothelial phenotype generated from adult peripheral blood have emerging diagnostic and therapeutic potential. This study examined the lineage relationship between, and angiogenic function of, early endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) in culture. Culture conditio...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000105569.77539.21

    authors: Gulati R,Jevremovic D,Peterson TE,Chatterjee S,Shah V,Vile RG,Simari RD

    更新日期:2003-11-28 00:00:00

  • Ventricular/vascular coupling and regional arterial dynamics in the chronically hypertensive baboon: correlation with cardiovascular structural adaptation.

    abstract::Ventricular/vascular coupling dynamics and regional hemodynamics of five hypertensive baboons with concentric left ventricular (LV) hypertrophy (mean arterial pressure +/- SD, 148 +/- 16 mm Hg; LV mass/body weight ratio 3.42 +/- 0.8) were compared with five normotensive controls (mean arterial pressure 89 +/- 3 mm Hg;...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.4.798

    authors: Latham RD,Rubal BJ,Sipkema P,Westerhof N,Virmani R,Robinowitz M,Walsh RA

    更新日期:1988-10-01 00:00:00

  • Differentiated Smooth Muscle Cells Generate a Subpopulation of Resident Vascular Progenitor Cells in the Adventitia Regulated by Klf4.

    abstract:RATIONALE:The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potenti...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.309322

    authors: Majesky MW,Horita H,Ostriker A,Lu S,Regan JN,Bagchi A,Dong XR,Poczobutt J,Nemenoff RA,Weiser-Evans MC

    更新日期:2017-01-20 00:00:00

  • Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction.

    abstract::To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.59.3.256

    authors: Tsunoda K,Hodsman GP,Sumithran E,Johnston CI

    更新日期:1986-09-01 00:00:00

  • Depletion of intracellular Ca2+ stores sensitizes the flow-induced Ca2+ influx in rat endothelial cells.

    abstract::Hemodynamic shear stress elicits a rise in endothelial [Ca2+]i, which may serve as a key second messenger to regulate many flow-associated physiological and biochemical processes. In the present study, we used Mn2+ quenching of fluorescent dye Fluo3 as an assay to investigate the Ca2+ influx of rat aortic endothelial ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000054625.24468.08

    authors: Kwan HY,Leung PC,Huang Y,Yao X

    更新日期:2003-02-21 00:00:00

  • Voltage-gated sodium channels are required for heart development in zebrafish.

    abstract:RATIONALE:Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. OBJECTIVE:Here we addressed this question b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.213132

    authors: Chopra SS,Stroud DM,Watanabe H,Bennett JS,Burns CG,Wells KS,Yang T,Zhong TP,Roden DM

    更新日期:2010-04-30 00:00:00

  • Voltage- and use-dependent effects of lidocaine on sodium current in rat single ventricular cells.

    abstract::We compared the blocking effects of the local anesthetics, lidocaine and benzocaine, on the sodium current, using single rat ventricular cells to obtain further information about the voltage dependence and kinetics of local anesthetic interaction with cardiac sodium channels. We used a hybrid voltage clamp system whic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.52.5.557

    authors: Sanchez-Chapula J,Tsuda Y,Josephson IR

    更新日期:1983-05-01 00:00:00

  • Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.

    abstract::A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription fac...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000127122.22685.0A

    authors: Marx N,Duez H,Fruchart JC,Staels B

    更新日期:2004-05-14 00:00:00

  • Animal model that mimics atherosclerotic plaque rupture.

    abstract::Atherosclerotic plaque rupture is the main cause of coronary thrombosis and myocardial infarcts. Currently, there is no animal model of plaque disruption. We have developed a rabbit model in which an atherosclerotic plaque can be ruptured at will after an inflatable balloon becomes embedded into the plaque. Furthermor...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.7.705

    authors: Rekhter MD,Hicks GW,Brammer DW,Work CW,Kim JS,Gordon D,Keiser JA,Ryan MJ

    更新日期:1998-10-05 00:00:00

  • Diabetes-induced vascular hypertrophy is accompanied by activation of Na(+)-H(+) exchange and prevented by Na(+)-H(+) exchange inhibition.

    abstract::Vascular disease often involves vessel hypertrophy with underlying cellular hypertrophy or hyperplasia. Experimental diabetes stimulates hypertrophy of the rat mesenteric vasculature, and we investigated the hypothesis that this hypertrophy is associated with activation of Na(+)-H(+) exchange (NHE) activity. We measur...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.12.1133

    authors: Jandeleit-Dahm K,Hannan KM,Farrelly CA,Allen TJ,Rumble JR,Gilbert RE,Cooper ME,Little PJ

    更新日期:2000-12-08 00:00:00

  • Transmural dispersion of repolarization in failing and nonfailing human ventricle.

    abstract:RATIONALE:Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.204891

    authors: Glukhov AV,Fedorov VV,Lou Q,Ravikumar VK,Kalish PW,Schuessler RB,Moazami N,Efimov IR

    更新日期:2010-03-19 00:00:00

  • Cholinergic constriction in the general circulation and its role in coronary artery spasm.

    abstract::The release of acetylcholine from autonomic nerves in those tissues that receive a cholinergic innervation is widely believed to dilate blood vessels. Exogenously administered acetylcholine in vivo does dilate vascular beds and produce hypotension; however, this latter effect is indirect and probably the result of lib...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.65.2.237

    authors: Kalsner S

    更新日期:1989-08-01 00:00:00

  • Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle.

    abstract::Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.3.585

    authors: Lab MJ,Lee JA

    更新日期:1990-03-01 00:00:00

  • Myofibroblasts induce ectopic activity in cardiac tissue.

    abstract::Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using st...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.107.160549

    authors: Miragoli M,Salvarani N,Rohr S

    更新日期:2007-10-12 00:00:00