Peroxisome proliferator-activated receptor alpha induces NADPH oxidase activity in macrophages, leading to the generation of LDL with PPAR-alpha activation properties.

Abstract:

:Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Different PPAR-alpha, but not PPAR-gamma agonists, increased the production of ROS (H2O2 and ) in human and murine macrophages. PPAR-alpha activation did not induce cellular toxicity, but significantly decreased intracellular glutathione levels. The increase in ROS production was not attributable to inherent prooxidant effects of the PPAR-alpha agonists tested, but was mediated by PPAR-alpha, because the effects were lost in bone marrow-derived macrophages from PPAR-alpha-/- mice. The PPAR-alpha-induced increase in ROS was attributable to the induction of NADPH oxidase, because (1) preincubation with the NADPH oxidase inhibitor diphenyleneiodinium prevented the increase in ROS production; (2) PPAR-alpha agonists increased production measured by superoxide dismutase-inhibitable cytochrome c reduction; (3) PPAR-alpha agonists induced mRNA levels of the NADPH oxidase subunits p47(phox), p67phox, and gp91phox and membrane p47phox protein levels; and (4) induction of ROS production was abolished in p47phox-/- and gp91phox-/- macrophages. Finally, induction of NADPH oxidase by PPAR-alpha agonists resulted in the formation of oxidized LDL metabolites that exert PPAR-alpha-independent proinflammatory and PPAR-alpha-dependent decrease of lipopolysaccharide-induced inducible nitric oxide synthase expression in macrophages. These data identify a novel mechanism of autogeneration of endogenous PPAR-alpha ligands via stimulation of NADPH oxidase activity.

journal_name

Circ Res

journal_title

Circulation research

authors

Teissier E,Nohara A,Chinetti G,Paumelle R,Cariou B,Fruchart JC,Brandes RP,Shah A,Staels B

doi

10.1161/01.RES.0000150594.95988.45

subject

Has Abstract

pub_date

2004-12-10 00:00:00

pages

1174-82

issue

12

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000150594.95988.45

journal_volume

95

pub_type

杂志文章
  • L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current.

    abstract::Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.70.3.456

    authors: Shorofsky SR,January CT

    更新日期:1992-03-01 00:00:00

  • Central nervous system mechanisms involved in inhibition of renal sympathetic nerve activity induced by arginine vasopressin.

    abstract::Previous studies have suggested that intravenous infusion of arginine vasopressin (AVP) inhibits sympathetic nerve activity (SNA) in rabbits by its action at the brainstem. This study aimed to determine, first, whether this action of AVP depended on functioning baroreflex mechanisms. The second aim was to determine th...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.5.1390

    authors: Suzuki S,Takeshita A,Imaizumi T,Hirooka Y,Yoshida M,Ando S,Nakamura M

    更新日期:1989-11-01 00:00:00

  • Is Optimism Associated With Healthier Cardiovascular-Related Behavior? Meta-Analyses of 3 Health Behaviors.

    abstract::Optimistic people have reduced risk for cardiovascular disease and cardiovascular-related mortality compared with their less optimistic peers. One explanation for this is that optimistic people may be more likely to engage in healthy behavior like exercising frequently, eating fruits and vegetables, and avoiding cigar...

    journal_title:Circulation research

    pub_type: 杂志文章,meta分析,评审

    doi:10.1161/CIRCRESAHA.117.310828

    authors: Boehm JK,Chen Y,Koga H,Mathur MB,Vie LL,Kubzansky LD

    更新日期:2018-04-13 00:00:00

  • 14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries.

    abstract::Endothelium-dependent hyperpolarization and relaxation of vascular smooth muscle are mediated by endothelium-derived hyperpolarizing factors (EDHFs). EDHF candidates include cytochrome P-450 metabolites of arachidonic acid, K(+), hydrogen peroxide, or electrical coupling through gap junctions. In bovine coronary arter...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000018162.87285.f8

    authors: Gauthier KM,Deeter C,Krishna UM,Reddy YK,Bondlela M,Falck JR,Campbell WB

    更新日期:2002-05-17 00:00:00

  • Developmental changes in the sensitivity of the chick embryo ventricle to beta-adrenergic agonist during adrenergic innervation.

    abstract::As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.2.245

    authors: Higgins D,Pappano AJ

    更新日期:1981-02-01 00:00:00

  • Hydrogen peroxide decreases pHi in human aortic endothelial cells by inhibiting Na+/H+ exchange.

    abstract::Postischemic endothelial dysfunction may occur as a result of the effects of endogenous oxidants like hydrogen peroxide. Since endothelium-dependent vasodilator function may be affected by pHi, the effect of hydrogen peroxide on endothelial pHi was examined. Hydrogen peroxide (100 micromol/L for 10 minutes) decreased ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.6.644

    authors: Hu Q,Xia Y,Corda S,Zweier JL,Ziegelstein RC

    更新日期:1998-09-21 00:00:00

  • Role of heart and lung receptors with nonmedullated vagal afferents in circulatory control.

    abstract::Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.38.6.2

    authors: Thorén PN,Donald DE,Shepherd JT

    更新日期:1976-06-01 00:00:00

  • Diminished Ca2+ sensitivity of skinned cardiac muscle contractility coincident with troponin T-band shifts in the diabetic rat.

    abstract::We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force re...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.76.4.600

    authors: Akella AB,Ding XL,Cheng R,Gulati J

    更新日期:1995-04-01 00:00:00

  • Prejunctional inhibition of norepinephrine release caused by acetylcholine in the human saphenous vein.

    abstract::We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.49.2.337

    authors: Rorie DK,Rusch NJ,Shepherd JT,Vanhoutte PM,Tyce GM

    更新日期:1981-08-01 00:00:00

  • Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro.

    abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.3.318

    authors: Weinberger MH,Aoi W,Henry DP

    更新日期:1975-09-01 00:00:00

  • Adenosine-induced vasoconstriction in vivo. Role of the mast cell and A3 adenosine receptor.

    abstract::Adenosine, a vasodilator metabolite, is often produced in tissues where the demand for oxygen exceeds the supply. We have recently demonstrated in isolated cannulated arterioles that adenosine and its metabolite, inosine, can also cause vasoconstriction by stimulation of mast cells. Secondary release of histamine and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.78.4.627

    authors: Shepherd RK,Linden J,Duling BR

    更新日期:1996-04-01 00:00:00

  • Metabolic Surgery for Hypertension in Patients With Obesity.

    abstract::The global prevalence of overweight and obesity has risen substantially over the past 4 decades and is accompanied by an increasing burden of cardiovascular risk factors such as hypertension. Metabolic surgery is the most effective method to treat obesity and may further improve associated conditions. Although most re...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.118.313320

    authors: Pareek M,Bhatt DL,Schiavon CA,Schauer PR

    更新日期:2019-03-29 00:00:00

  • Direct vasoconstriction evoked by A1-adenosine receptor stimulation in the cutaneous microcirculation.

    abstract::To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused the release of other substances or whether A1 stimulation modulated the vasoconstriction evoked by other compounds, a potent A1-selective, synthetic agonist, cyclohexyladenosine (CHA), was topically app...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.3.683

    authors: Proctor KG,Stojanov I

    更新日期:1991-03-01 00:00:00

  • Epigenetic regulation of pluripotency and differentiation.

    abstract::The precise, temporal order of gene expression during development is critical to ensure proper lineage commitment, cell fate determination, and ultimately, organogenesis. Epigenetic regulation of chromatin structure is fundamental to the activation or repression of genes during embryonic development. In recent years, ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.115.301517

    authors: Boland MJ,Nazor KL,Loring JF

    更新日期:2014-07-07 00:00:00

  • Ventricular pressure-volume curve indices change with end-diastolic pressure.

    abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.6.772

    authors: Glantz SA

    更新日期:1976-12-01 00:00:00

  • Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter.

    abstract::The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.192443

    authors: Horsthuis T,Buermans HP,Brons JF,Verkerk AO,Bakker ML,Wakker V,Clout DE,Moorman AF,'t Hoen PA,Christoffels VM

    更新日期:2009-07-02 00:00:00

  • Gene transfer into normal and atherosclerotic human blood vessels.

    abstract::Gene transfer to blood vessels is a promising new approach to the treatment of the vascular diseases, but the feasibility of gene transfer to adult human vessels has not been explored. We introduced an adenovirus vector encoding a marker gene human placental alkaline phosphatase into normal and atherosclerotic human v...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.12.1243

    authors: Rekhter MD,Simari RD,Work CW,Nabel GJ,Nabel EG,Gordon D

    更新日期:1998-06-29 00:00:00

  • Failure of atriopeptin II to cause arterial vasodilation in the conscious rat.

    abstract::The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.56.4.606

    authors: Lappe RW,Smits JF,Todt JA,Debets JJ,Wendt RL

    更新日期:1985-04-01 00:00:00

  • Reactive oxygen species production in energized cardiac mitochondria during hypoxia/reoxygenation: modulation by nitric oxide.

    abstract::Mitochondria are an important source of reactive oxygen species (ROS), implicated in ischemia/reperfusion injury. When isolated from ischemic myocardium, mitochondria demonstrate increased ROS production as a result of damage to electron transport complexes. To investigate the mechanisms, we studied effects of hypoxia...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.180869

    authors: Korge P,Ping P,Weiss JN

    更新日期:2008-10-10 00:00:00

  • Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor.

    abstract::Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electric abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focu...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.110.223842

    authors: Moore JR,Leinwand L,Warshaw DM

    更新日期:2012-07-20 00:00:00

  • Relative roles of cardiac and arterial baroreceptors in vasopressin regulation during hemorrhage in conscious dogs.

    abstract::To determine the relative roles of cardiac and sinoaortic baroreceptors in mediation of arginine vasopressin (AVP) release, hemorrhage was performed in five groups of conscious splenectomized dogs: 1) all nerves intact; 2) either chronic surgical or acute pharmacological (intrapericardial lidocaine) cardiac denervatio...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.5.1422

    authors: Shen YT,Cowley AW Jr,Vatner SF

    更新日期:1991-05-01 00:00:00

  • Electrotonic interactions across an inexcitable region as a cause of ectopic activity in acute regional myocardial ischemia. A study in intact porcine and canine hearts and computer models.

    abstract::We recorded 60 DC simultaneous electrograms from isolated porcine and canine hearts in the first minutes after coronary occlusion. Ventricular premature beats (VPB) originated from the normal side of the ischemic border, which was frequently separated from the central ischemic area showing delayed activity by a small ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.50.4.527

    authors: Janse MJ,van Capelle FJ

    更新日期:1982-04-01 00:00:00

  • Comparison of the effects of different inotropic interventions on force, velocity, and power in rabbit myocardium.

    abstract::To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.5.1161

    authors: Chiu YC,Walley KR,Ford LE

    更新日期:1989-11-01 00:00:00

  • New Insights Into the Role of mTOR Signaling in the Cardiovascular System.

    abstract::The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR co...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.117.311147

    authors: Sciarretta S,Forte M,Frati G,Sadoshima J

    更新日期:2018-02-02 00:00:00

  • Historical perspective on the pathology of myocardial ischemia/reperfusion injury.

    abstract::A selective history of the pathophysiological, structural, and metabolic changes found during an episode of severe myocardial ischemia in the canine heart is presented. The changes that cause ischemic injury to become irreversible are discussed in detail because these changes are the target of any successful therapy d...

    journal_title:Circulation research

    pub_type: 历史文章,杂志文章,评审

    doi:10.1161/CIRCRESAHA.113.300987

    authors: Jennings RB

    更新日期:2013-08-02 00:00:00

  • Angiogenesis and pericytes in the initiation of ectopic calcification.

    abstract::Ectopic calcification of blood vessels, heart valves, and skeletal muscle is a major clinical problem. There is now good evidence that angiogenesis is associated with ectopic calcification in these tissues and that it is necessary, but not sufficient, for calcification to occur. Angiogenesis may regulate ectopic calci...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000163634.51301.0d

    authors: Collett GD,Canfield AE

    更新日期:2005-05-13 00:00:00

  • Heteromultimeric TRPC6-TRPC7 channels contribute to arginine vasopressin-induced cation current of A7r5 vascular smooth muscle cells.

    abstract::The molecular identity of receptor-operated, nonselective cation channels (ROCs) of vascular smooth muscle (VSM) cells is not known for certain. Mammalian homologues of the Drosophila canonical transient receptor potential channels (TRPCs) are possible candidates. This study tested the hypothesis that heteromultimeric...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000226495.34949.28

    authors: Maruyama Y,Nakanishi Y,Walsh EJ,Wilson DP,Welsh DG,Cole WC

    更新日期:2006-06-23 00:00:00

  • Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.

    abstract:RATIONALE:Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors. OBJECTIVE:Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist. METHO...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.118.314416

    authors: Myagmar BE,Ismaili T,Swigart PM,Raghunathan A,Baker AJ,Sahdeo S,Blevitt JM,Milla ME,Simpson PC

    更新日期:2019-09-13 00:00:00

  • Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts.

    abstract::Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-ma...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.5.975

    authors: Vogel WM,Apstein CS

    更新日期:1988-05-01 00:00:00

  • Reduced reperfusion-induced Ins(1,4,5)P3 generation and arrhythmias in hearts expressing constitutively active alpha1B-adrenergic receptors.

    abstract::Reperfusion of globally ischemic rat hearts causes the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and the initiation of arrhythmias. These responses are mediated by alpha1-adrenergic receptors (ARs), but the subtype of receptor involved has not been identified. Under normoxic conditions, hearts from tra...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.12.1232

    authors: Harrison SN,Autelitano DJ,Wang BH,Milano C,Du XJ,Woodcock EA

    更新日期:1998-12-14 00:00:00