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Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors.

Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Research Abstract Details 

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  • Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Abstract Text:

     pacher Pacher,csaba Csaba , pacher Pacher,csaba Csaba , pacher Pacher,csaba Csaba ,pál pacherPál Pacher,csaba szabóCsaba Szabó,

    Accumulating evidence suggests that the reactive oxygen and nitrogen species are generated in cardiomyocytes and endothelial cells during myocardial ischemia/reperfusion injury, various forms of heart failure or cardiomyopathies, circulatory shock, cardiovascular aging, diabetic complications, myocardial hypertrophy, atherosclerosis, and vascular remodeling following injury. These reactive species induce oxidative DNA damage and consequent activation of the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), the most abundant isoform of the PARP enzyme family. PARP overactivation, on the one hand, depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to the functional impairment or death of the endothelial cells and cardiomyocytes. On the other hand, PARP activation modulates important inflammatory pathways, and PARP-1 activity can also be modulated by several endogenous factors such as various kinases, purines, vitamin D, thyroid hormones, polyamines, and estrogens, just to mention a few. Recent studies have demonstrated that pharmacological inhibition of PARP provides significant benefits in animal models of cardiovascular disorders, and novel PARP inhibitors have entered clinical development for various cardiovascular indications. Because PARP inhibitors can enhance the effect of anticancer drugs and decrease angiogenesis, their therapeutic potential is also being explored for cancer treatment. This review discusses the therapeutic effects of PARP inhibitors in myocardial ischemia/reperfusion injury, various forms of heart failure, cardiomyopathies, circulatory shock, cardiovascular aging, diabetic cardiovascular complications, myocardial hypertrophy, atherosclerosis, vascular remodeling following injury, angiogenesis, and also summarizes our knowledge obtained from the use of PARP-1 knockout mice in the various preclinical models of cardiovascular diseases.

    Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Publishing Authors By Initials

    p pacherP Pacher,c C ,p pacherP Pacher,c C ,p pacherP Pacher,c C ,p pacherP Pacher,c szabóC Szabó,

    For similar abstracts research abstracts see: abstracts research

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    Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Intr

    Journal: Cardiovascular drug reviews

    VOLUME: 25

    Page Numbers: 235-60

    Journal Abbreviation:

    ISSN: 0897-5957

    DAY: 8

    MONTH: 10

    YEAR: 2007

    Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Information

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    LANGUAGE: eng

    NlmUniqueID: 9006912

    Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Keywords Mesh Terms:

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    Grant and Affiliation Information for Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors.

    AFFILIATION: Section on Oxidative Stress and Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health, NIAAA, Bethesda MD 20892-9413, USA. pacher@mail.nih.gov

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIGMS

    GRANT: R01 GM060915

    ACRONYM: GM

    MEDLINETA: Cardiovasc Drug Rev

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