Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome.


:Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by TNF-alpha overexpression. To test this, we measured endothelium-dependent (acetylcholine) and -independent vasodilation (sodium nitroprusside) of isolated, pressurized coronary small arteries from lean control and Zucker obese fatty (ZOF, a model of prediabetic metabolic syndrome) rats. In ZOF rats, dilation to ACh was blunted compared with lean rats, but sodium nitroprusside-induced dilation was comparable. Superoxide (O2*-) generation was elevated in vessels from ZOF rats compared with lean rats, and administration of the O2*- scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF-alpha restored endothelium-dependent dilation in the ZOF rats. Real-time PCR and Western blotting revealed that mRNA and protein of TNF-alpha were higher in ZOF rats than that in lean rats, whereas eNOS protein levels were reduced in the ZOF versus lean rats. Immunostaining showed that TNF-alpha in ZOF rat heart is localized in endothelial cells and vascular smooth muscle cells. Expression of NAD(P)H subunits p22 and p40-phox were elevated in ZOF compared with lean animals. Administration of TNF-alpha more than 3 days also induced expression of these NAD(P)H subunits and abrogated endothelium-dependent dilation. In conclusion, the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine TNF-alpha and subsequent production of O2*-.


Circ Res


Circulation research


Picchi A,Gao X,Belmadani S,Potter BJ,Focardi M,Chilian WM,Zhang C




Has Abstract


2006-07-07 00:00:00














  • Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2.

    abstract:RATIONALE:Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with t...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zoccarato A,Surdo NC,Aronsen JM,Fields LA,Mancuso L,Dodoni G,Stangherlin A,Livie C,Jiang H,Sin YY,Gesellchen F,Terrin A,Baillie GS,Nicklin SA,Graham D,Szabo-Fresnais N,Krall J,Vandeput F,Movsesian M,Furlan L,Corse

    更新日期:2015-09-25 00:00:00

  • Lidocaine action on Na+ currents in ventricular myocytes from the epicardial border zone of the infarcted heart.

    abstract::Myocytes overlying a zone of infarction form the primary substrate for serious reentrant ventricular arrhythmias. In vitro and in vivo studies suggest that antiarrhythmic agents affect Na+ channels of cells from the epicardial border zone (EBZ) of the 5-day infarcted heart differently than they affect those of normal ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Pu J,Balser JR,Boyden PA

    更新日期:1998-08-24 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


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

    更新日期:1983-05-01 00:00:00

  • A 17mer peptide interferes with acidification-induced uncoupling of connexin43.

    abstract::Structure/function analysis shows that the carboxyl terminal (CT) domain of connexin43 (Cx43) is essential for the chemical regulation of cell-cell communication. Of particular interest is the region between amino acids 260 and 300. Structural preservation of this region is essential for acidification-induced uncoupli...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Calero G,Kanemitsu M,Taffet SM,Lau AF,Delmar M

    更新日期:1998-05-18 00:00:00

  • Disease pathways and novel therapeutic targets in hypertrophic cardiomyopathy.

    abstract::As described in earlier reviews in this series on the molecular basis of hypertrophic cardiomyopathy (HCM), HCM is one of the archetypal monogenic cardiovascular disorders to be understood at the molecular level. Twenty years after the discovery of the first HCM disease gene, genetic studies still confirm that HCM is ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Ashrafian H,McKenna WJ,Watkins H

    更新日期:2011-06-24 00:00:00

  • Hypertension, transmural pressure, and vascular smooth muscle response in rats.

    abstract::The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pr...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hansen TR,Bohr DF

    更新日期:1975-05-01 00:00:00

  • Alteration of endothelium-dependent hyperpolarizations in porcine coronary arteries with regenerated endothelium.

    abstract::The present study was designed to test the ability of regenerated endothelium to evoke endothelium-dependent hyperpolarizations. Hyperpolarizations induced by serotonin and bradykinin were compared in isolated porcine coronary arteries with native or regenerated endothelium, 4 weeks after balloon endothelial denudatio...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Thollon C,Bidouard JP,Cambarrat C,Delescluse I,Villeneuve N,Vanhoutte PM,Vilaine JP

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  • Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration.

    abstract::Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development of atherosclerosis. However, the factors present within lesions that mediate VSMC phenotypic switching are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosp...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Cherepanova OA,Pidkovka NA,Sarmento OF,Yoshida T,Gan Q,Adiguzel E,Bendeck MP,Berliner J,Leitinger N,Owens GK

    更新日期:2009-03-13 00:00:00

  • Progestogens do not affect aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits.

    abstract::Cardiovascular disease is a major killer in postmenopausal women in the industrialized societies. To investigate the effect of progestogen and 17 beta-estradiol replacement therapy on atherogenesis, we studied 60 cholesterol-fed ovariectomized rabbits for 13 weeks. They were randomly assigned to four groups of 15 rabb...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Haarbo J,Svendsen OL,Christiansen C

    更新日期:1992-06-01 00:00:00

  • Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products.

    abstract::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Yeh M,Cole AL,Choi J,Liu Y,Tulchinsky D,Qiao JH,Fishbein MC,Dooley AN,Hovnanian T,Mouilleseaux K,Vora DK,Yang WP,Gargalovic P,Kirchgessner T,Shyy JY,Berliner JA

    更新日期:2004-10-15 00:00:00

  • Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here?

    abstract::In the mammalian myocardium, potassium (K(+)) channels control resting potentials, action potential waveforms, automaticity, and refractory periods and, in most cardiac cells, multiple types of K(+) channels that subserve these functions are expressed. Molecular cloning has revealed the presence of a large number of K...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Nerbonne JM,Nichols CG,Schwarz TL,Escande D

    更新日期:2001-11-23 00:00:00

  • Coronary artery spasm in intact dogs induced by potassium and serotonin.

    abstract::Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were appl...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Pérez JE,Saffitz JE,Gutiérrez FA,Henry PD

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  • Clock genes in the heart: characterization and attenuation with hypertrophy.

    abstract::We investigated whether the heart, like other mammalian organs, possesses internal clocks, and, if so, whether pressure overload-induced hypertrophy alters the clock mechanism. Clock genes are intrinsically maintained, as shown by rhythmic changes even in single cells. Clocks are believed to confer a selective advanta...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Young ME,Razeghi P,Taegtmeyer H

    更新日期:2001-06-08 00:00:00

  • Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice.

    abstract:RATIONALE:The mechanisms driving atherothrombotic risk in individuals with JAK2 V617F ( Jak2 VF) positive clonal hematopoiesis or myeloproliferative neoplasms are poorly understood. OBJECTIVE:The goal of this study was to assess atherosclerosis and underlying mechanisms in hypercholesterolemic mice with hematopoietic ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wang W,Liu W,Fidler T,Wang Y,Tang Y,Woods B,Welch C,Cai B,Silvestre-Roig C,Ai D,Yang YG,Hidalgo A,Soehnlein O,Tabas I,Levine RL,Tall AR,Wang N

    更新日期:2018-11-09 00:00:00

  • Role of 14-3-3-mediated p38 mitogen-activated protein kinase inhibition in cardiac myocyte survival.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zhang S,Ren J,Zhang CE,Treskov I,Wang Y,Muslin AJ

    更新日期:2003-11-28 00:00:00

  • Dopamine attenuates the contractile response to angiotensin II in isolated rat glomeruli and cultured mesangial cells.

    abstract::Recent evidence suggests that dopamine may alter kidney function by actions not only in the renal vasculature but also at the glomerular-mesangial level. We studied this phenomenon by examining the ability of dopamine to antagonize the contractile properties of angiotensin II in isolated rat glomeruli and cultured mes...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Barnett R,Singhal PC,Scharschmidt LA,Schlondorff D

    更新日期:1986-11-01 00:00:00

  • Dynamic changes in the canine mitral regurgitant orifice area during ventricular ejection.

    abstract::We designed this study to test the hypothesis that in acute mitral regurgitation the mitral regurgitant area (MRA) is a dynamic quantity which varies with the time variation of ventricular volume. Mitral insufficiency was created in five open-chest dogs in which a portion of the anterior leaflet was excised. Phasic ao...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Yellin EL,Yoran C,Sonnenblick EH,Gabbay S,Frater RW

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  • Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium.

    abstract::Abnormalities of myocardial gap junction-mediated cell coupling have been implicated in cardiac arrhythmogenesis. The potential role of gap junctional dysfunction in the generation of reperfusion-induced arrhythmias is uncertain. The purpose of this study was to measure the effects of myocardial ischemia and reperfusi...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Kieval RS,Spear JF,Moore EN

    更新日期:1992-07-01 00:00:00

  • High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system.

    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


    authors: Tamaddon HS,Vaidya D,Simon AM,Paul DL,Jalife J,Morley GE

    更新日期:2000-11-10 00:00:00

  • Defect in microvascular adaptation to chronic changes in blood flow in mice lacking the gene encoding for dystrophin.

    abstract::Dystrophin has a key role in striated muscle mechanotransduction. In mice lacking the gene encoding for dystrophin (mdx mice), the absence of dystrophin and several other proteins of the dystrophin-glycoprotein complex induces a defect in flow (shear stress)-mediated NO-dependent dilation (FMD). Because the endotheliu...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Loufrani L,Levy BI,Henrion D

    更新日期:2002-12-13 00:00:00

  • Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.

    abstract::In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Myers BD,Deen WM,Brenner BM

    更新日期:1975-07-01 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


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

    更新日期:2012-01-06 00:00:00

  • Mobilization of bone marrow-derived cells enhances the angiogenic response to hypoxia without transdifferentiation into endothelial cells.

    abstract::Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: O'Neill TJ 4th,Wamhoff BR,Owens GK,Skalak TC

    更新日期:2005-11-11 00:00:00

  • Hypoxia regulates bone morphogenetic protein signaling through C-terminal-binding protein 1.

    abstract::Bone morphogenetic protein receptor 2 (BMPR2) mutations have been linked to familial pulmonary arterial hypertension (PAH), but the molecular pathways leading to this severe pathology remain poorly characterized. We report that hypoxia, a paramount stimulus for the development of pulmonary hypertension, suppresses the...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wu X,Chang MS,Mitsialis SA,Kourembanas S

    更新日期:2006-08-04 00:00:00

  • Atrial fibrillation in KCNE1-null mice.

    abstract::Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1, one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show h...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Temple J,Frias P,Rottman J,Yang T,Wu Y,Verheijck EE,Zhang W,Siprachanh C,Kanki H,Atkinson JB,King P,Anderson ME,Kupershmidt S,Roden DM

    更新日期:2005-07-08 00:00:00

  • Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance.

    abstract::We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We o...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Liao D,Tan H,Hui R,Li Z,Jiang X,Gaubatz J,Yang F,Durante W,Chan L,Schafer AI,Pownall HJ,Yang X,Wang H

    更新日期:2006-09-15 00:00:00

  • Analysis of systolic bulging. Mechanical characteristics of acutely ischemic myocardium in the conscious dog.

    abstract::To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent s...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Akaishi M,Weintraub WS,Schneider RM,Klein LW,Agarwal JB,Helfant RH

    更新日期:1986-02-01 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


    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

  • Antagonistic modulatory roles of magnesium and calcium on release of endothelium-derived relaxing factor and smooth muscle tone.

    abstract::The objective of this study was to elucidate the mechanisms associated with the reciprocal relation between magnesium and calcium on vascular smooth muscle tone in bovine pulmonary artery and vein. Rapid removal of magnesium from Krebs-bicarbonate medium used to bathe isolated rings of precontracted artery or vein cau...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Gold ME,Buga GM,Wood KS,Byrns RE,Chaudhuri G,Ignarro LJ

    更新日期:1990-02-01 00:00:00

  • Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure.

    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


    authors: Zhang P,Xu X,Hu X,van Deel ED,Zhu G,Chen Y

    更新日期:2007-04-13 00:00:00