Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction.

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Abstract Text:

Radovits,Leila Seres,Domokos Gero,Irina Berger,Csaba ,Matthias Karck, , Radovits,Leila Seres,Domokos Gero,Irina Berger,Csaba ,Matthias Karck, ,

Overproduction of reactive oxygen species in aging tissues has been implicated in the pathogenesis of aging-associated cardiovascular dysfunction. Oxidant-induced DNA-damage activates the poly(ADP-ribose) polymerase (PARP) pathway, leading to tissue injury. In this study we investigated the acute effects of the PARP inhibitor INO-1001 on aging-associated cardiac and endothelial dysfunction. Using a pressure-volume conductance catheter, left ventricular pressure-volume analysis of young and aging rats was performed before and after a single injection of INO-1001. Endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine and sodium nitroprusside. Aging animals showed a marked reduction of myocardial contractility and endothelium-dependent relaxant responsiveness of aortic rings. Single dose INO-1001-treatment resulted in acute improvement in their cardiac and endothelial function. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) confirmed enhanced nitro-oxidative stress and PARP-activation in aging animals. Acute treatment with INO-1001 decreased PARP-activation, but did not affect nitrotyrosine-immunoreactivity. Our results demonstrate that the aging-associated chronic cardiovascular dysfunction can be improved, at least, short term, by a single treatment course with a PARP-inhibitor, supporting the role of the nitro-oxidative stress -- PARP -- pathway in the age-related functional decline of the cardiovascular system. Pharmacological inhibition of PARP may represent a novel therapeutic utility to improve aging-associated cardiovascular dysfunction.

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Publishing Authors By Initials

T Radovits,L Seres,D Gero,I Berger,C ,M Karck,G ,T Radovits,L Seres,D Gero,I Berger,C ,M Karck,G ,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Journal Published:

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

Journal: Experimental gerontology

VOLUME: 42

Page Numbers: 676-85

Journal Abbreviation: Exp. Gerontol.

ISSN: 0531-5565

DAY: 20

MONTH: 02

YEAR: 2007

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 47061

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction.

AFFILIATION: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, Heidelberg, Germany. radovitstamas@yahoo.com

Country: England

AGENCY: United States NIGMS

GRANT: R01 GM060915

ACRONYM: GM

MEDLINETA: Exp Gerontol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction Related Publications

• 5'- O -Demethylnarcotine: A New Alkaloid from Papaver somniferum.
• A phase I study of myo-inositol for lung cancer chemoprevention.
• A time-resolved fluorescence study of 4',6'-diamidine-2-phenylindole dihydrochloride binding to polynucleotides.
• Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes.
• Activation of the poly(ADP-ribose) polymerase pathway in human heart failure.
• Acute alcohol activates STAT3, AP-1, and Sp-1 transcription factors via the family of Src kinases to promote IL-10 production in human monocytes.
• Antiandrogenic effect of isotretinoin: Is the retina involved in mechanism of action?
• Bipolar saline TURP for large prostate glands.
• Characterization of Staphylococcus aureus strains isolated from bovine milk in Hungary.
• Competing associations in bacterial warfare with two toxins.
• Computer-aided spectrophotometric determination of multicomponent drugs.
• Cosegregation of gastrointestinal ulcers and schizophrenia in a large national inpatient discharge database: revisiting the "brain-gut axis" hypothesis in ulcer pathogenesis.
• Critical role of toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury.
• Effects of 7-ketocholesterol on the activity of endothelial poly(ADP-ribose) polymerase and on endothelium-dependent relaxant function.
• Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection.
• Local administration of the poly(ADP-ribose) polymerase inhibitor INO-1001 prevents NAD+ depletion and improves water maze performance after traumatic brain injury in mice.
• Long-term outcomes of dorsal intercarpal ligament capsulodesis for chronic scapholunate dissociation.
• MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis.
• Model-Based Receptor Quantization Analysis for PET Parametric Imaging.
• Oxidant-induced cardiomyocyte injury: identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay.
• Petasis Borono-Mannich reaction and allylation of carbonyl compounds via transient allyl boronates generated by palladium-catalyzed substitution of allyl alcohols. an efficient one-pot route to stereodefined alpha-amino acids and homoallyl alcohols.
• Poly(ADP-Ribose) polymerase inhibition improves endothelial dysfunction induced by hypochlorite.
• Poly(ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by reactive oxidant hydrogen peroxide in vitro.
• Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA.
• Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors.
• Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction.
• Single nucleotide polymorphism: is it only genetic palmistry?
• Single-molecule FRET with diffusion and conformational dynamics.
• The association between the anti-inflammatory protein CC10 and smoking status among participants in a chemoprevention trial.
• Viral and host factors induce macrophage activation and loss of toll-like receptor tolerance in chronic HCV infection.