Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

Abstract:

RATIONALE:There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD). OBJECTIVE:We aimed to discover new biomarkers associated with doxorubicin- and trastuzumab-induced CTRCD using high-throughput proteomic profiling. METHODS AND RESULTS:Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubicin and trastuzumab cancer therapy. Thirty-one longitudinal plasma samples from 3 cases with CTRCD and 4 age- and cancer-matched controls without CTRCD were processed and analyzed using label-free liquid chromatography-mass spectrometry. From these analyses, 862 proteins were identified from case/control pairs 1 and 2 and 1360 proteins from case/control pair 3. Proteins with a >1.5-fold change in cases compared with controls with a P<0.05 either at the time of CTRCD diagnosis or across all time points were considered candidate diagnostic or predictive biomarkers, respectively. The protein that demonstrated the largest differences between cases and controls was immunoglobulin E, with higher levels detected at baseline and across all time points in controls without CTRCD as compared with matched CTRCD cases (P<0.05). Similarly, in a validation study of 35 participants treated with doxorubicin and trastuzumab, high baseline immunoglobulin E levels were associated with a significantly lower risk of CTRCD (P=0.018). CONCLUSIONS:In patients receiving doxorubicin and trastuzumab, high baseline immunoglobulin E levels are associated with a lower risk of CTRCD. These novel findings suggest a new paradigm in cardio-oncology, implicating the immune system as a potential mediator of doxorubicin- and trastuzumab-induced cardiac dysfunction.

journal_name

Circ Res

journal_title

Circulation research

authors

Beer LA,Kossenkov AV,Liu Q,Luning Prak E,Domchek S,Speicher DW,Ky B

doi

10.1161/CIRCRESAHA.116.309004

subject

Has Abstract

pub_date

2016-10-28 00:00:00

pages

1135-1144

issue

10

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.116.309004

journal_volume

119

pub_type

杂志文章
  • The role of adenosine in prolonged vasodilation following flow-restricted exercise of canine skeletal muscle.

    abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.44.6.759

    authors: Belloni FL,Phair RD,Sparks HV

    更新日期:1979-06-01 00:00:00

  • Stress, deformation, and atelectasis of the lung.

    abstract::The lung parenchyma as a tissue has a rather unusual stress-strain relationship. A theoretical derivation of this relationship is presented which connects the surface tension and the tissue elastic stress in the alveolar septa with the alveolar geometry. The mathematical expression contains a few meaningful physical c...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.4.481

    authors: Fung YC

    更新日期:1975-10-01 00:00:00

  • Altered cardiac responsiveness and regulation in the normal cardiac output type of borderlind hlpertension.

    abstract::Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.36.6.199

    authors: Julius S,Randall OS,Esler MD,Kashima T,Ellis C,Bennett J

    更新日期:1975-06-01 00:00:00

  • Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation.

    abstract:RATIONALE:Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. OBJECTIVE:The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.302439

    authors: Wang Y,Wang X,Lau WB,Yuan Y,Booth D,Li JJ,Scalia R,Preston K,Gao E,Koch W,Ma XL

    更新日期:2014-02-28 00:00:00

  • Platelet-activating factor and the release of a platelet-derived coronary artery vasodilator substance in the canine.

    abstract::Platelet-activating factor (acetyl-glyceryl-ether-phosphorylcholine; 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine), which is released by stimulated neutrophils and platelets, possesses the ability to alter vascular tone and permeability and to activate various formed blood elements. We have characterized the he...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.58.2.218

    authors: Jackson CV,Schumacher WA,Kunkel SL,Driscoll EM,Lucchesi BR

    更新日期:1986-02-01 00:00:00

  • Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in normal porcine aortic valves.

    abstract::Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000161998.92009.64

    authors: Simmons CA,Grant GR,Manduchi E,Davies PF

    更新日期:2005-04-15 00:00:00

  • Mitogenic effect of angiotensin II on rat carotid arteries and type II or III mesenteric microvessels but not type I mesenteric microvessels is mediated by endogenous basic fibroblast growth factor.

    abstract::In this study, anti-basic fibroblast growth factor (anti-bFGF) antibody was used to determine whether the mitogenic effect of angiotensin II in vivo could be blocked by neutralizing bFGF in the vessel wall. Animals, divided into six experimental groups, were given (1) angiotensin II, (2) angiotensin II + anti-bFGF ant...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.82.3.321

    authors: Su EJ,Lombardi DM,Wiener J,Daemen MJ,Reidy MA,Schwartz SM

    更新日期:1998-02-23 00:00:00

  • Specific induction of tie1 promoter by disturbed flow in atherosclerosis-prone vascular niches and flow-obstructing pathologies.

    abstract::Nonlaminar flow is a major predisposing factor to atherosclerosis. Yet little is known regarding hemodynamic gene regulation in disease-prone areas of the vascular tree in vivo. We have determined spatial patterns of expression of endothelial cell receptors in the arterial tree and of reporter gene constructs in trans...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000111803.92923.D6

    authors: Porat RM,Grunewald M,Globerman A,Itin A,Barshtein G,Alhonen L,Alitalo K,Keshet E

    更新日期:2004-02-20 00:00:00

  • Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure.

    abstract:RATIONALE:It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE:The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS:In 110 patients with systolic heart failu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307765

    authors: Parisi V,Rengo G,Perrone-Filardi P,Pagano G,Femminella GD,Paolillo S,Petraglia L,Gambino G,Caruso A,Grimaldi MG,Baldascino F,Nolano M,Elia A,Cannavo A,De Bellis A,Coscioni E,Pellegrino T,Cuocolo A,Ferrara N,Leosco D

    更新日期:2016-04-15 00:00:00

  • Glycogen synthase kinase 3beta inhibits myocardin-dependent transcription and hypertrophy induction through site-specific phosphorylation.

    abstract::Cardiomyocyte hypertrophy is transcriptionally controlled and inhibited by glycogen synthase kinase 3beta (GSK3beta). Myocardin is a muscle-specific transcription factor with yet unknown relation to hypertrophy. Therefore, we investigated whether myocardin is sufficient to induce cardiomyocyte hypertrophy and whether ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000184684.88750.FE

    authors: Badorff C,Seeger FH,Zeiher AM,Dimmeler S

    更新日期:2005-09-30 00:00:00

  • Relation between lipopolysaccharide-induced endothelial cell injury and entry of macromolecules into the rat aorta in vivo.

    abstract::Lipopolysaccharide (LPS) causes endothelial cell injury both in vitro and in vivo. It is widely believed that this injury in vivo enhances the transport of macromolecules from plasma into the interstitial space of the underlying artery wall. A new technique was used in rats to obtain high resolution transmural profile...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.5.1259

    authors: Penn MS,Chisolm GM

    更新日期:1991-05-01 00:00:00

  • MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction.

    abstract::Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myoc...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000118597.54416.00

    authors: van Rooij E,Doevendans PA,Crijns HJ,Heeneman S,Lips DJ,van Bilsen M,Williams RS,Olson EN,Bassel-Duby R,Rothermel BA,De Windt LJ

    更新日期:2004-02-20 00:00:00

  • The interferon stimulated gene 12 inactivates vasculoprotective functions of NR4A nuclear receptors.

    abstract:RATIONALE:Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. OBJECTIVE:The underlying mechanisms that regulate the activity of NR4A1 during vascula...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.258814

    authors: Papac-Milicevic N,Breuss JM,Zaujec J,Ryban L,Plyushch T,Wagner GA,Fenzl S,Dremsek P,Cabaravdic M,Steiner M,Glass CK,Binder CJ,Uhrin P,Binder BR

    更新日期:2012-04-13 00:00:00

  • Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

    abstract:RATIONALE:Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse. OBJECTIVE:This study sought to explore the premise that ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317293

    authors: Davidson MT,Grimsrud PA,Lai L,Draper JA,Fisher-Wellman KH,Narowski TM,Abraham DM,Koves TR,Kelly DP,Muoio DM

    更新日期:2020-09-25 00:00:00

  • 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

    doi:10.1161/hh1101.091190

    authors: Young ME,Razeghi P,Taegtmeyer H

    更新日期:2001-06-08 00:00:00

  • Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.

    abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.57.1.182

    authors: Neely BH,Urthaler F,Hageman GR

    更新日期:1985-07-01 00:00:00

  • Dominant negative suppression of Rad leads to QT prolongation and causes ventricular arrhythmias via modulation of L-type Ca2+ channels in the heart.

    abstract::Disorders of L-type Ca2+ channels can cause severe cardiac arrhythmias. A subclass of small GTP-binding proteins, the RGK family, regulates L-type Ca2+ current (I(Ca,L)) in heterologous expression systems. Among these proteins, Rad (Ras associated with diabetes) is highly expressed in the heart, although its role in t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.106.146399

    authors: Yada H,Murata M,Shimoda K,Yuasa S,Kawaguchi H,Ieda M,Adachi T,Murata M,Ogawa S,Fukuda K

    更新日期:2007-07-06 00:00:00

  • Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine Models.

    abstract:RATIONALE:Monocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.118.312804

    authors: Kim K,Shim D,Lee JS,Zaitsev K,Williams JW,Kim KW,Jang MY,Seok Jang H,Yun TJ,Lee SH,Yoon WK,Prat A,Seidah NG,Choi J,Lee SP,Yoon SH,Nam JW,Seong JK,Oh GT,Randolph GJ,Artyomov MN,Cheong C,Choi JH

    更新日期:2018-10-26 00:00:00

  • Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in x-ray-irradiated hypercholesterolemic pigs.

    abstract::To assess whether coronary spasm affects the progression of atherosclerosis and results in evolution of myocardial infarction, the role of coronary spasm on the fine structure of conduit coronary arteries was studied morphologically. Göttingen miniature pigs were fed a semisynthetic diet containing 2% cholesterol and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.2.272

    authors: Nagasawa K,Tomoike H,Hayashi Y,Yamada A,Yamamoto T,Nakamura M

    更新日期:1989-08-01 00:00:00

  • Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.

    abstract::Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (T...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.107.150474

    authors: Henke N,Schmidt-Ullrich R,Dechend R,Park JK,Qadri F,Wellner M,Obst M,Gross V,Dietz R,Luft FC,Scheidereit C,Muller DN

    更新日期:2007-08-03 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

  • Hypercholesterolemia suppresses inwardly rectifying K+ channels in aortic endothelium in vitro and in vivo.

    abstract::Inwardly rectifying K+ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000218776.87842.43

    authors: Fang Y,Mohler ER 3rd,Hsieh E,Osman H,Hashemi SM,Davies PF,Rothblat GH,Wilensky RL,Levitan I

    更新日期:2006-04-28 00:00:00

  • Mechanism of the serotonin effect on lung transvascular fluid and protein movement in awake sheep.

    abstract::To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin e...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.36.6.761

    authors: Brigham KL,Owen PJ

    更新日期:1975-06-01 00:00:00

  • Blood pressure and vascular resistance in genetically hypertensive rats treated at birth with 6-hydroxydopamine.

    abstract::Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.43.2.293

    authors: Clark DW,Jones DR,Phelan EL,Devine CE

    更新日期:1978-08-01 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

  • Flow-related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells.

    abstract::In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.4.827

    authors: Prasad AR,Logan SA,Nerem RM,Schwartz CJ,Sprague EA

    更新日期:1993-04-01 00:00:00

  • Apoptosis during cardiovascular development.

    abstract::Morphogenesis and developmental remodeling of cardiovascular tissues involve coordinated regulation of cell proliferation and apoptosis. In the heart, clear evidence points toward focal apoptosis as a contributor to development of the embryonic outflow tract, cardiac valves, conducting system, and the developing coron...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.87.10.856

    authors: Fisher SA,Langille BL,Srivastava D

    更新日期:2000-11-10 00:00:00

  • Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression.

    abstract::Vascular smooth muscle cell (VSMC) proliferation is a critical event in the development and progression of vascular diseases, including atherosclerosis. We investigated whether the activation of adenosine monophosphate-activated protein kinase (AMPK) could suppress VSMC proliferation and inhibit cell cycle progression...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000185823.73556.06

    authors: Igata M,Motoshima H,Tsuruzoe K,Kojima K,Matsumura T,Kondo T,Taguchi T,Nakamaru K,Yano M,Kukidome D,Matsumoto K,Toyonaga T,Asano T,Nishikawa T,Araki E

    更新日期:2005-10-14 00:00:00

  • Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.

    abstract:RATIONALE:Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. OBJECTIVE:We tested the hypothesis that removal of a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.305518

    authors: Conklin DJ,Guo Y,Jagatheesan G,Kilfoil PJ,Haberzettl P,Hill BG,Baba SP,Guo L,Wetzelberger K,Obal D,Rokosh DG,Prough RA,Prabhu SD,Velayutham M,Zweier JL,Hoetker JD,Riggs DW,Srivastava S,Bolli R,Bhatnagar A

    更新日期:2015-08-14 00:00:00

  • The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis.

    abstract::In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimula...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.303577

    authors: Prabhu SD,Frangogiannis NG

    更新日期:2016-06-24 00:00:00