Molecular and cellular mechanisms of cardiotoxicity

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Cardiotoxicity resulting from detrimental environmental insults has been recognized for a long time. However, extensive studies of the mechanisms involved had not been undertaken until recent years. Advances in molecular biology provide powerful tools and make such studies possible. We are gathering information about cellular events, signaling pathways, and molecular mechanisms of myocardial toxicologic responses to environmental toxicants and pollutants. Severe acute toxic insults cause cardiac cell death instantly. In the early response to mild environmental stimuli, biochemical changes such as alterations in calcium homeostasis occur. These may lead to cardiac arrhythmia, which most often is reversible. Prolonged stimuli activate transcription factors such as activator protein-1 through elevation of intracellular calcium and the subsequent activation of calcineurin. Upregulation by activated transcription factors of hypertrophic genes results in heart hypertrophy, which is a short-term adaptive response to detrimental factors. However, further development of hypertrophy will lead to severe and irreversible cardiomyopathy, and eventually heart failure. From cardiac hypertrophy to heart failure, myocardial cells undergo extensive biochemical and molecular changes. Cardiac hypertrophy causes tissue hypoperfusion, which activates compensatory mechanisms such as production of angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy and, importantly, activate counterregulatory mechanisms including overexpression of atrial natriuretic peptide and b-type natriuretic peptide, and production of cytokines such as tumor necrosis factor-α. This counterregulation leads to myocardial remodeling as well as cell death through apoptosis and necrosis. Cell death through activation of mitochondrial factors and other pathways constitutes an important cellular mechanism of heart failure. Our current knowledge of cardiotoxicity is limited. Further extensive studies are warranted for a comprehensive understanding of this field.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalEnvironmental Health Perspectives
Volume109
Issue numberSUPPL. 1
StatePublished - Apr 26 2001

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Cardiomegaly
Cell Death
Heart Failure
Transcription Factors
Calcium
Environmental Pollutants
Natriuretic Peptides
Calcineurin
Poisons
Transcription Factor AP-1
Atrial Natriuretic Factor
Cardiomyopathies
Angiotensin II
Hypertrophy
Cardiac Arrhythmias
Molecular Biology
Norepinephrine
Homeostasis
Necrosis
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Molecular and cellular mechanisms of cardiotoxicity. / Kang, Yujian.

In: Environmental Health Perspectives, Vol. 109, No. SUPPL. 1, 26.04.2001, p. 27-34.

Research output: Contribution to journalArticle

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