Activation of vascular bone morphogenetic protein signaling in diabetes mellitus.

Abstract:

RATIONALE:Diabetes mellitus is frequently complicated by cardiovascular disease, such as vascular calcification and endothelial dysfunction, which have been associated with bone morphogenetic proteins (BMPs). OBJECTIVE:To determine whether hyperglycemia in vitro and diabetes in vivo promote vascular BMP activity and correlate with vascular calcification. METHODS AND RESULTS:Increased glucose augmented expression of BMP-2 and BMP-4; the BMP inhibitors matrix Gla protein (MGP) and Noggin; activin-like kinase receptor (ALK)1, -2, -3 and -6; the BMP type 2 receptor; and the vascular endothelial growth factor in human aortic endothelial cells (HAECs). Diabetes induced expression of the same factors in the aortic wall of 3 animal models of diabetes, Ins2(Akita/+) mice, db/db mice, and HIP rats (rats transgenic for human islet amyloid polypeptide), representative of types 1 and 2 diabetes. Conditioned media from glucose-treated HAECs increased angiogenesis in bovine aortic endothelial cells, as mediated by BMP-4, and osteogenesis in calcifying vascular cells, as mediated by BMP-2. BMP-4, MGP, ALK1, and ALK2 were predominantly expressed on the endothelial side of the aorta, and small interfering RNA experiments showed that these genes were regulated as a group. Diabetic mice and rats showed a dramatic increase in aortic BMP activity, as demonstrated by SMAD1/5/8 phosphorylation. This was associated with increased osteogenesis and calcium accumulation. These changes were prevented in the Ins2(Akita/+) mice by breeding them with MGP transgenic mice, which increased aortic BMP inhibition. CONCLUSIONS:Hyperglycemia and diabetes activate vascular BMP activity, which is instrumental in promoting vascular calcification and may be limited by increasing BMP inhibition.

journal_name

Circ Res

journal_title

Circulation research

authors

Boström KI,Jumabay M,Matveyenko A,Nicholas SB,Yao Y

doi

10.1161/CIRCRESAHA.110.236596

subject

Has Abstract

pub_date

2011-02-18 00:00:00

pages

446-57

issue

4

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.110.236596

journal_volume

108

pub_type

杂志文章
  • MicroRNA regulation of cardiovascular development.

    abstract::The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving posttranscriptional regulation by small, noncod...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.108.192872

    authors: Cordes KR,Srivastava D

    更新日期:2009-03-27 00:00:00

  • The effect of hypophysectomy on experimental endothelial cell regrowth and intimal thickening in the rat.

    abstract::We studied the influence of hypophysectomy on endothelial cell regrowth and intimal thickening following aortic endothelial removal. Modification of this influence by replacement doses of glucocorticoids, mineralocorticoids, thyroxin, and growth hormone also was investigated. Young adult male rats were used, and endot...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.6.907

    authors: Bettmann MA,Stemerman MB,Ransil BJ

    更新日期:1981-06-01 00:00:00

  • Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium.

    abstract::Experiments were designed to determine the contribution of endothelial cells to the heterogeneous behavior of the arterial and venous wall. Rings of canine femoral, pulmonary, saphenous, and splenic arteries and veins, with and without endothelium, were mounted for isometric tension recording in Krebs-Ringer bicarbona...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.51.4.439

    authors: De Mey JG,Vanhoutte PM

    更新日期:1982-10-01 00:00:00

  • Alpha1-adrenergic stimulation of sarcolemmal Na+-H+ exchanger activity in rat ventricular myocytes: evidence for selective mediation by the alpha1A-adrenoceptor subtype.

    abstract::Alpha1-adrenoceptor (alpha1-AR) stimulation increases sarcolemmal Na+-H+ exchanger (NHE) activity. The present study was designed to determine the role(s) of alpha1-AR subtype(s) in mediating this response. As an index of NHE activity, acid efflux rates (JHs) were determined in single rat ventricular myocytes loaded w...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.10.1078

    authors: Yokoyama H,Yasutake M,Avkiran M

    更新日期:1998-06-01 00:00:00

  • The distribution of refractory periods influences the dynamics of ventricular fibrillation.

    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

    authors: Choi BR,Liu T,Salama G

    更新日期:2001-03-16 00:00:00

  • Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors.

    abstract::Endothelial cells release several compounds, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF), that mediate the vascular effects of vasoactive hormones. The identity of EDHF remains unknown. Since arachidonic acid causes endothelium-dependent relaxations of coronary arteries through it...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.78.3.415

    authors: Campbell WB,Gebremedhin D,Pratt PF,Harder DR

    更新日期:1996-03-01 00:00:00

  • Unspliced XBP1 Confers VSMC Homeostasis and Prevents Aortic Aneurysm Formation via FoxO4 Interaction.

    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

    authors: Zhao G,Fu Y,Cai Z,Yu F,Gong Z,Dai R,Hu Y,Zeng L,Xu Q,Kong W

    更新日期:2017-12-08 00:00:00

  • Spread of contraction in rabbit ear artery preparations in response to stimulation by norepinephrine.

    abstract::To investigate the spread of contraction in the rabbit ear artery, changes in segment diameter were measured after local stimulation. No spread of contraction was produced by direct current or local application of norepinephrine (NE). Repetitive electrical stimulation caused contraction which spread far from the point...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.49.3.600

    authors: Vonderlage M

    更新日期:1981-09-01 00:00:00

  • Stem cells as a source of regenerative cardiomyocytes.

    abstract::The realization of regenerative cardiac medicine depends on the availability of cardiomyocytes in sufficient numbers for transplantation of cardiac tissue and the accompanying blood vessels. Embryonic stem (ES) cells, bone marrow (BM) stem cells, and tissue-derived stem cells are all potential cell sources. Although E...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000218272.18669.6e

    authors: Fukuda K,Yuasa S

    更新日期:2006-04-28 00:00:00

  • Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling.

    abstract:RATIONALE:Transcatheter, intramyocardial injections of bone marrow-derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. OBJECTIVE:We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothes...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.242610

    authors: Williams AR,Trachtenberg B,Velazquez DL,McNiece I,Altman P,Rouy D,Mendizabal AM,Pattany PM,Lopera GA,Fishman J,Zambrano JP,Heldman AW,Hare JM

    更新日期:2011-04-01 00:00:00

  • Selective Targeting of a Novel Epsin-VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis.

    abstract:RATIONALE:We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the mole...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307679

    authors: Rahman HNA,Wu H,Dong Y,Pasula S,Wen A,Sun Y,Brophy ML,Tessneer KL,Cai X,McManus J,Chang B,Kwak S,Rahman NS,Xu W,Fernandes C,Mcdaniel JM,Xia L,Smith L,Srinivasan RS,Chen H

    更新日期:2016-03-18 00:00:00

  • Muscarinic-activated K+ current in bovine aortic endothelial cells.

    abstract::Isolated, cultured arterial endothelial cells express an acetylcholine (ACh)-activated K+ current in addition to an inward rectifier current whose conductance is unaffected by ACh. The cholinergic K+ current is specifically blocked by atropine (1 microM) and shows single saturation kinetics with ACh (half-maximal stim...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.6.1059

    authors: Olesen SP,Davies PF,Clapham DE

    更新日期:1988-06-01 00:00:00

  • The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase.

    abstract::Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.86.5.580

    authors: Kantor PF,Lucien A,Kozak R,Lopaschuk GD

    更新日期:2000-03-17 00:00:00

  • High-resolution 3-dimensional reconstruction of the infarct border zone: impact of structural remodeling on electrical activation.

    abstract:RATIONALE:Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) can give rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear. OBJECTIVE:To determine whether structural remodeling alone in the i...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.260943

    authors: Rutherford SL,Trew ML,Sands GB,LeGrice IJ,Smaill BH

    更新日期:2012-07-20 00:00:00

  • cdc25A is necessary but not sufficient for optimal c-myc-induced apoptosis and cell proliferation of vascular smooth muscle cells.

    abstract::Increasing evidence indicates that the control of cell proliferation and apoptosis are linked. The c-myc proto-oncogene is induced early after cell-cycle entry in vascular smooth muscle cells (VSMCs) in vitro and after arterial injury and regulates both cell proliferation and apoptosis. Although both proliferation and...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.84.7.820

    authors: Macdonald K,Bennett MR

    更新日期:1999-04-16 00:00:00

  • The recovery time course of the endothelial cell glycocalyx in vivo and its implications in vitro.

    abstract::Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the g...

    journal_title:Circulation research

    pub_type: 评论,杂志文章

    doi:10.1161/CIRCRESAHA.108.191585

    authors: Potter DR,Jiang J,Damiano ER

    更新日期:2009-06-05 00:00:00

  • Inflammation in myocardial diseases.

    abstract::Inflammatory processes underlie a broad spectrum of conditions that injure the heart muscle and cause both structural and functional deficits. In this article, we address current knowledge regarding 4 common forms of myocardial inflammation: myocardial ischemia and reperfusion, sepsis, viral myocarditis, and immune re...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.111.243170

    authors: Marchant DJ,Boyd JH,Lin DC,Granville DJ,Garmaroudi FS,McManus BM

    更新日期:2012-01-06 00:00:00

  • Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells.

    abstract::We examined the role of endogenous NO in the autonomic regulation of atrioventricular (AV) nodal function by studying spontaneous action potentials (SAPs) and L-type Ca2+ current (ICa-L) in isolated single AV nodal cells from adult rabbit hearts. Both the perforated and the membrane-ruptured patch-clamp techniques in ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.78.6.998

    authors: Han X,Kobzik L,Balligand JL,Kelly RA,Smith TW

    更新日期:1996-06-01 00:00:00

  • Decreased atrial natriuretic peptide binding in renal medulla in rats with chronic heart failure.

    abstract::The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantit...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.1.155

    authors: Tsunoda K,Mendelsohn FA,Sexton PM,Chai SY,Hodsman GP,Johnston CI

    更新日期:1988-01-01 00:00:00

  • A new method of measuring propagation coefficients and characteristic impedance in blood vessels.

    abstract::True propagation coefficients of pulse wave harmonics in an artery can be determined in vivo by measuring pulsatile blood pressure and flow at each of two points along the length of the vessel. These coefficients, which are complex numbers that describe the attenuation and the phase shift imposed on a traveling wave, ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.36.5.631

    authors: Milnor WR,Nichols WW

    更新日期:1975-05-01 00:00:00

  • Tra2beta as a novel mediator of vascular smooth muscle diversification.

    abstract::Transformer splicing regulatory proteins determine the sexually dimorphic traits of Drosophila. The role of the vertebrate homologs of Tra-2 in phenotypic specification is undefined. We are using the alternative splicing of the MYPT1 E23 exon as a model for the study of smooth muscle diversification into fast and slow...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.178384

    authors: Shukla S,Fisher SA

    更新日期:2008-08-29 00:00:00

  • Upregulation of alveolar epithelial active Na+ transport is dependent on beta2-adrenergic receptor signaling.

    abstract::Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechani...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000125623.56442.20

    authors: Mutlu GM,Dumasius V,Burhop J,McShane PJ,Meng FJ,Welch L,Dumasius A,Mohebahmadi N,Thakuria G,Hardiman K,Matalon S,Hollenberg S,Factor P

    更新日期:2004-04-30 00:00:00

  • Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression.

    abstract::Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.70.3.593

    authors: Rao GN,Berk BC

    更新日期:1992-03-01 00:00:00

  • Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle.

    abstract::Bone morphogenetic peptides (BMPs), a family of cytokines critical to normal development, were recently implicated in the pathogenesis of familial pulmonary arterial hypertension. The type-II receptor (BMPRII) is required for recognition of all BMPs, and targeted deletion of BMPRII in mice results in fetal lethality b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000126047.82846.20

    authors: West J,Fagan K,Steudel W,Fouty B,Lane K,Harral J,Hoedt-Miller M,Tada Y,Ozimek J,Tuder R,Rodman DM

    更新日期:2004-04-30 00:00:00

  • Species-specific differences in positive and negative regulatory elements in the renin gene enhancer.

    abstract::A distal transcriptional enhancer has been previously reported upstream of the mouse renin gene. A homologous sequence is also present upstream of the human renin gene, but the mouse and human renin enhancers differ markedly in their ability to activate transcription of a renin promoter. Although the 2 enhancers share...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.85.6.479

    authors: Shi Q,Black TA,Gross KW,Sigmund CD

    更新日期:1999-09-17 00:00:00

  • Regulation of oxygen distribution in tissues by endothelial nitric oxide.

    abstract::Nitric oxide (NO) decreases cellular oxygen (O(2)) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O(2) consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.197228

    authors: Victor VM,Nuñez C,D'Ocón P,Taylor CT,Esplugues JV,Moncada S

    更新日期:2009-05-22 00:00:00

  • Stroke Caused by Atherosclerosis of the Major Intracranial Arteries.

    abstract::Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and int...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.308441

    authors: Banerjee C,Chimowitz MI

    更新日期:2017-02-03 00:00:00

  • Adeno-associated virus-mediated transduction of VEGF165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs.

    abstract::We have previously shown that VEGF165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. The aim of this study was to determine whether recombinant adeno-associated virus (rAAV)-mediated gene delivery of VEGF165 into cardiac muscle...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000217342.83731.89

    authors: Ferrarini M,Arsic N,Recchia FA,Zentilin L,Zacchigna S,Xu X,Linke A,Giacca M,Hintze TH

    更新日期:2006-04-14 00:00:00

  • Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products.

    abstract:RATIONALE:Oxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty ac...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.305925

    authors: Kim YW,Yakubenko VP,West XZ,Gugiu GB,Renganathan K,Biswas S,Gao D,Crabb JW,Salomon RG,Podrez EA,Byzova TV

    更新日期:2015-07-31 00:00:00

  • PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.

    abstract:RATIONALE:PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. OBJECTIVE:Here...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.119.316063

    authors: Rykaczewska U,Suur BE,Röhl S,Razuvaev A,Lengquist M,Sabater-Lleal M,van der Laan SW,Miller CL,Wirka RC,Kronqvist M,Gonzalez Diez M,Vesterlund M,Gillgren P,Odeberg J,Lindeman JH,Veglia F,Humphries SE,de Faire U,Baldass

    更新日期:2020-02-28 00:00:00