Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin.

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Abstract Text:

Tomas G Neilan,Sarah L Blake,Fumito Ichinose,Michael J Raher,Emmanuel S Buys,Davinder S Jassal,Elissa Furutani,Teresa Miriam Perez-Sanz,Amanda Graveline,Stefan P Janssens,Michael H Picard,Marielle Scherrer-Crosbie,Kenneth D Bloch,

BACKGROUND: Flavoprotein reductases are involved in the generation of reactive oxygen species by doxorubicin. The objective of the present study was to determine whether or not one flavoprotein reductase, endothelial nitric oxide synthase (nitric oxide synthase 3 [NOS3]), contributes to the cardiac dysfunction and injury seen after the administration of doxorubicin. METHODS AND RESULTS: A single dose of doxorubicin (20 mg/kg) was administered to wild-type (WT) mice, NOS3-deficient mice (NOS3-/-), and mice with cardiomyocyte-specific overexpression of NOS3 (NOS3-TG). Cardiac function was assessed after 5 days with the use of echocardiography. Doxorubicin decreased left ventricular fractional shortening from 57+/-2% to 47+/-1% (P<0.001) in WT mice. Compared with WT mice, fractional shortening was greater in NOS3-/- and less in NOS3-TG after doxorubicin (55+/-1% and 35+/-2%; P<0.001 for both). Cardiac tissue was harvested from additional mice at 24 hours after doxorubicin administration for measurement of cell death and reactive oxygen species production. Doxorubicin induced cardiac cell death and reactive oxygen species production in WT mice, effects that were attenuated in NOS3-/- and were more marked in NOS3-TG mice. Finally, WT and NOS3-/- mice were treated with a lower dose of doxorubicin (4 mg/kg) administered weekly over 5 weeks. Sixteen weeks after beginning doxorubicin treatment, fractional shortening was greater in NOS3-/- than in WT mice (45+/-2% versus 28+/-1%; P<0.001), and mortality was reduced (7% versus 60%; P<0.001). CONCLUSIONS: These findings implicate NOS3 as a key mediator in the development of left ventricular dysfunction after administration of doxorubicin.

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Publishing Authors By Initials

TG Neilan,SL Blake,F Ichinose,MJ Raher,ES Buys,DS Jassal,E Furutani,TM Perez-Sanz,A Graveline,SP Janssens,MH Picard,M Scherrer-Crosbie,KD Bloch,

For similar cardiovascular diseases: heart diseases: ventricular dysfunction: ventricular dysfunction, left research abstracts see: cardiovascular diseases: heart diseases: ventricular dysfunction: ventricular dysfunction, left research

PUBMED ID PMID:

MEDLINE DATE:

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Circulation

VOLUME: 116

Page Numbers: 506-14

Journal Abbreviation: Circulation

ISSN: 1524-4539

DAY: 16

MONTH: 07

YEAR: 2007

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 147763

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Keywords Mesh Terms:

KEYWORDS: Ventricular Dysfunction, Left

MESH TERMS: ultrasonography

Chemical & Substance for Abstract: Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Information

Substance Name: Nos3 protein, mouse

Registry Number: EC 1.14.13.39

Grant and Affiliation Information for Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin.

AFFILIATION: Cardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Charlestown, MA, USA. tneilan@partners.org

Country: United States

AGENCY: United States NHLBI

GRANT: HL-71987

ACRONYM: HL

MEDLINETA: Circulation

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin Related Publications

• A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence.
• Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy.
• Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization.
• Controlling for occasion-specific effects when assessing the test-retest reliability of self-report health questionnaires.
• Daytime Cheyne-Stokes respiration in ambulatory patients with severe congestive heart failure is associated with increased mortality.
• Delayed Recovery Of Skeletal Muscle Function In Dysferlin- deficient Mice Following Large-strain Lengthening Contractions: 1857: Board #145 May 31 9:00 AM - 10:30 AM.
• Demonstration of presence of acanthamoeba mitochondrial DNA in brain tissue and cerebrospinal fluid by PCR in samples from a patient who died of granulomatous amebic encephalitis.
• Different obscurin isoforms localize to distinct sites at sarcomeres.
• Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin.
• Extracorporeal circulation activates endothelial nitric oxide synthase in erythrocytes.
• Influence Of An Interdisciplinary Programme Adipocytokines And Insulin Resistance In Obese Children And Adolescence: 1502: Board #265 May 30 9:30 AM - 11:00 AM.
• Mapping the binding site on small ankyrin 1 for obscurin.
• Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock.
• Obscurin: a multitasking muscle giant.
• Probing the mRNA processing body using protein macroarrays and "autoantigenomics".
• Substance abuse among medical practitioners.
• THE CONTRIBUTION OF MICROSCOPES TO THE STUDY OF LIVING CIRCULATION: NEWER METHODS FOR THE STUDY OF DYNAMIC EVENTS IN LIVING ORGANS.
• Tailoring peripartum nursing care for women of advanced maternal age.
• The actin binding domain of ACF7 binds directly to the tetratricopeptide repeat domains of rapsyn.
• The art of psychiatry.
• Transzygomatic approach to the tentorial incisura: surgical anatomy.
• Value of the 12-lead resting electrocardiogram for the diagnosis of previous myocardial infarction in paced patients.
• [A new operative procedure for the treatment of urinary incontinence]
• [Consequence of GKV-WSG for physicians' remuneration. Facts--analyses--perspectives]
• [Hemoptysis after subclavian vein puncture]
• [Modalities of the early development of the embryo and nidation in mammals]
• [On the problem of gland cells in the uterine muscles in women]
• [Studies on the influence of estrogen on ovum implantation in mice]
• [Treatment of so-called functional uterine hemorrhages]
• cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein.