Oxidative stress and apoptosis in heart dysfunction

Herz. 2002 Nov;27(7):662-8. doi: 10.1007/s00059-002-2430-3.

Abstract

Background: Heart disease is a major cause of morbidity and mortality due to its complex pathogenesis. Myocyte cell loss through apoptosis has been reported in a variety of cardiovascular disease conditions including myocardial infarction (MI), ischemia-reperfusion injury, end-stage heart failure and adriamycin cardiomyopathy.

Potential apoptotic factors and therapeutic target: The cell biology of the apoptotic regulatory processes and the precise role of apoptosis in the development of cardiac dysfunction need to be established. The upregulation of proapoptic proteins, like Bax (a member of the Bcl-2 family proteins), caspases and cytochrome c, with or without the downregulation of antiapoptic proteins, including Bcl-2 (another member of the Bcl family), Akt and inhibitory apoptotic proteins (IAPs), has been documented in different cardiac disease conditions. However, mitogen-activated protein kinases (MAPKs) have been shown to be involved in both apoptosis and cell survival. Apoptosis can be blocked by inhibiting apoptotic regulatory pathways with caspase inhibitors and overexpression of Bcl-2 and Akt. More recently, increased oxidative stress has been shown to promote apoptosis, and antioxidants have been shown to inhibit this process.

Conclusion: The ability of antioxidants to inhibit these apoptotic pathways has raised the possibility of newer therapeutic treatment for various heart diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis* / drug effects
  • Apoptosis* / physiology
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Cell Death
  • Cell Survival
  • Cells, Cultured
  • DNA Fragmentation
  • Doxorubicin / toxicity
  • Heart Diseases / drug therapy*
  • Heart Diseases / etiology*
  • Heart Diseases / metabolism
  • Heart Diseases / pathology
  • Heart Failure / etiology
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Humans
  • Mitogen-Activated Protein Kinases / physiology
  • Myocardial Infarction / etiology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardium / pathology
  • Myocytes, Cardiac / cytology
  • Necrosis
  • Oxidative Stress* / drug effects
  • Rabbits
  • Rats
  • Reactive Oxygen Species
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Time Factors

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Reactive Oxygen Species
  • Doxorubicin
  • Mitogen-Activated Protein Kinases