title: Oxidative stress and apoptosis in heart dysfunction.
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.
  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.
  
  
  CONCLUSIONS
  The ability of antioxidants to inhibit these apoptotic pathways has raised the possibility of newer therapeutic treatment for various heart diseases.
authors.affiliation: Cardiovascular Research Group, Department of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: Dinender
authors.initials: D
authors.lastname: Kumar
authors.forename: Huiquan
authors.initials: H
authors.lastname: Lou
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Singal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004317:Doxorubicin / Q000633:toxicity; D006331:Heart Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D020928:Mitogen-Activated Protein Kinases