Oxidative Stress and Heart Failure

Q. M. Chen, S. Morrissy, J. S. Alpert

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Heart failure is an end point of many types of heart disease. Although symptoms or cardiac structure may differ among individuals or stages of heart failure, the most common clinic presentation of heart failure involves reduced excise tolerance, elevated blood levels of B-type natriuretic peptide (BNP), and reduced cardiac output. Among the common causes of heart failure are unmanaged hypertension, ischemia, valvular disease, myocarditis and toxin induced cardiomyopathy. Morphologically failing hearts show enlarged cardiomyocytes and apoptosis of a small fraction of cardiomyocytes. In parallel with these changes in cardiomyocytes, fibrosis is evident with proliferation of fibroblasts and altered secretion of extracellular matrix proteins. The progression of heart failure is usually related to activation of neurohormonal and renin-angiotensin-aldosterone systems, resulting in increased circulating levels of catecholamines and angiotensin II. Catecholamines or angiotensin II binds to adrenergic receptors or angiotensin receptor, respectively, in the plasma membrane of cardiomyocytes to initiate a cascade of signaling events regulating contraction-relaxation coupling. Chronic activation of adrenergic or angiotensin II signaling contributes to cardiac remodeling, cardiomyocyte hypertrophy, and heart failure. While catecholamines can undergo auto-oxidation to generate free radicals, angiotensin II produces reactive oxygen species (ROS) following receptor binding and activation of a membrane associated NAD(P)H oxidase. Additional sources of oxidants include ischemia, ischemic reperfusion, drugs undergoing redox cycling, and an inflammatory response. Whereas ROS are known to induce apoptosis and have been shown to play a role in fibrosis, recent evidence suggests that ROS contribute to hypertrophy of cardiomyocytes. Measurements of biomarkers of oxidative stress have indicated an association with heart failure. Transgenic animals null in antioxidant enzymes show increased cardiac injury following ischemia and reperfusion, while overexpression of antioxidant enzymes or proteins protects the heart from various types of heart failure inducers. Several pharmacological agents currently used for the treatment of heart failure, such as ACE inhibitors captopril and ramipril, angiotensin receptor blocker telmisartan, aldosterone receptor antagonist eplerenone, and blockers nebivolol and carvedilol, exhibit antioxidant activity. However, clinical trials of antioxidant vitamins have failed to show clear prevention against heart failure or reduction of the mortality rate associated with heart failure. Therefore, the ultimate role of ROS in heart failure requires further investigation.

Original languageEnglish (US)
Title of host publicationCardiovascular Toxicology
PublisherElsevier Inc.
Pages230-251
Number of pages22
Volume13-15
ISBN (Electronic)9780081006122
ISBN (Print)9780081006016
DOIs
StatePublished - Jan 1 2018

Keywords

  • Angiotensin II
  • Antioxidant enzymes
  • Antioxidant vitamins
  • Apoptosis
  • Cardiomyopathy
  • Catecholamines
  • Doxorubicin
  • Fatty acids
  • Fibrosis
  • Hypertrophy
  • Ischemia
  • Muscle proteins
  • Pharmacological agents
  • Signal transduction pathways
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)

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    Chen, Q. M., Morrissy, S., & Alpert, J. S. (2018). Oxidative Stress and Heart Failure. In Cardiovascular Toxicology (Vol. 13-15, pp. 230-251). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-801238-3.65249-2