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Poly(ADP-Ribose) Polymerase Activation and Nitrosative Stress in the Development of Cardiovascular Disease in Diabetes

  • Chapter
Diabetes and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Macro- and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus (DM). Diabetic vascular dysfunction is a major clinical problem, which underlies the development of various severe complications including retinopathy, nephropathy, neuropathy, and increase the risk of stroke, hypertension, and myocardial infarction (MI). Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with oxidative and nitrosative stress, which can trigger the development of cardiovascular disease. Recently, emerging experimental and clinical evidence indicates that high-circulating glucose in DM is able to induce oxidative and nitrosative stress in the cardiovascular system, with the concomitant activation of an abundant nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP). This process results in acute loss of the ability of the endothelium to generate nitric oxide (NO; endothelial dysfunction) and also leads to a severe functional impairment of the diabetic heart (diabetic cardiomyopathy). Accordingly, neutralization of peroxynitrite or pharmacological inhibition of PARP protect against diabetic cardiovascular dysfunction. The goal of this chapter is to summarize the recently emerging evidence supporting the concept that nitrosative stress and PARP activation play a role in the pathogenesis of diabetic endothelial dysfunction and cardiovascular complications.

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Authors and Affiliations

  1. Inotek Pharmaceuticals, Beverly, MA

    Pál Pacher MD, PhD & Csaba Szabó MD, PhD

  2. Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD

    Pál Pacher MD, PhD

  3. Institute of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

    Pál Pacher MD, PhD

  4. Department of Human Physiology and Experimental Research, Semmelweis University, Budapest, Hungary

    Csaba Szabó MD, PhD

Authors
  1. Pál Pacher MD, PhD
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  2. Csaba Szabó MD, PhD
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Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Michael T. Johnstone MD, CM, FRCP(C)  & Aristidis Veves MD, DSC  & 

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© 2005 Humana Press Inc., Totowa, NJ

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Pacher, P., Szabó, C. (2005). Poly(ADP-Ribose) Polymerase Activation and Nitrosative Stress in the Development of Cardiovascular Disease in Diabetes. In: Johnstone, M.T., Veves, A. (eds) Diabetes and Cardiovascular Disease. Contemporary Cardiology. Humana Press. https://doi.org/10.1385/1-59259-908-7:167

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  • DOI: https://doi.org/10.1385/1-59259-908-7:167

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-413-5

  • Online ISBN: 978-1-59259-908-0

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