Oxidative Stress and Heart Failure

S. Morrissy, Qin Chen

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 clinical presentation of heart failure involves reduced exercise tolerance, elevated blood levels of B-type natriuretic peptide (BNP), and reduced cardiac output. Unmanaged hypertension, ischemia, valvular disease, myocarditis, and toxin-induced cardiomyopathy are the common causes of heart failure. Morphologically, failing hearts show enlarged cardiomyocytes, and apoptosis of a small fraction of cardiomyocytes has also been detected. In parallel with these changes of cardiomyocytes, fibrosis is evident as proliferation of fibroblasts and altered secretion of extracellular matrix protein. The progression of heart failure is often related to activation of neurohormonal and renin-angiotensin-aldosterone systems, resulting in increased levels of catecholamines and angiotensin II. Catecholamines bind to -adrenergic receptors 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 autooxidation to generate free radicals, angiotensin II produces reactive oxygen species (ROS) following receptor binding and activation of a membrane-associated nicotinamide adenine dinucleotide phosphate (reduced form) (NAD(P)H) oxidase. Additional sources of oxidants include ischemia and reperfusion injury, drugs undergoing redox cycling, and inflammatory response. 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 for antioxidant enzymes show increased cardiac injury consequential to 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 treatment of heart failure, such as angiotensin-converting enzyme (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 clearly show their role in the prevention of heart failure or reduction of the mortality rate associated with heart failure. Therefore, the role of ROS in heart failure remains to be investigated.

Original languageEnglish (US)
Title of host publicationCardiovascular Toxicology
PublisherElsevier Inc.
Pages221-242
Number of pages22
Volume6
ISBN (Print)9780080468686
DOIs
StatePublished - Aug 12 2010

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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