Molecular mechanisms of cardiac hypertrophy induced by toxicants.

Qin Chen, V. C. Tu, S. Purdon, J. Wood, T. Dilley

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Cardiac hypertrophy is an end point of chronic cardiac toxicity from a number of toxicants. Doxorubicin, cocaine, acetaldehyde, monocrotaline, and azide are examples of these toxicants, which may induce hypertrophy by increasing oxidants, circulating levels of catecholamines, and hemodynamic load or by inducing hypoxia. We summarize here the major signal transduction pathways and common changes in gene expression found with the classical hypertrophy inducers angiotensin II, endothelin 1, and catecholamines. Activation of G-proteins, calcium signaling, phosphoinositide 3-kinase (PI3K), certain family members of protein kinase Cs (PKCs), and three branches of mitogenactivated protein kinases (MAPKs), i.e. extracellular signal-regulated kinases (ERKs), p38, and c-Jun N-terminal kinases (JNKs), are important for developing a hypertrophic phenotype in cardiomyocytes. Characteristic changes of gene expression in hypertrophy include the elevated transcription of atrial natriuretic factor (ANF), beta-myosin heavy chain (beta MHC), skeletal alpha-actin (SkA), certain variants of integrins and perhaps tubulin genes, and reduced expression of the sarcoplasmic reticulum proteins phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPase 2 alpha (SERCA2 alpha), and of the ryanodine receptors. Although which toxicants induce these molecular changes remains to be tested, increasing lines of evidence support that oxidants play a central role in cardiac hypertrophy. Oxidants activate small G-proteins, calcium signaling, PI3K, PKCs, and MAPKs. Oxidants cause cardiomyocytes to enlarge in vitro. Recent developments in transgenic, genomic, and proteomic technologies will provide needed tools to reveal the mechanism of chronic cardiac toxicity at the cellular and molecular levels.

Original languageEnglish (US)
Pages (from-to)267-283
Number of pages17
JournalCardiovascular Toxicology
Volume1
Issue number4
StatePublished - 2001

Fingerprint

Cardiomegaly
Oxidants
Protein Kinases
Hypertrophy
1-Phosphatidylinositol 4-Kinase
Calcium Signaling
Phosphatidylinositols
Gene Expression
Cardiac Myocytes
Gene expression
Catecholamines
Toxicity
Monocrotaline
Calcium
Ventricular Myosins
Signal transduction
Reticulum
Ryanodine Receptor Calcium Release Channel
Monomeric GTP-Binding Proteins
Azides

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine

Cite this

Chen, Q., Tu, V. C., Purdon, S., Wood, J., & Dilley, T. (2001). Molecular mechanisms of cardiac hypertrophy induced by toxicants. Cardiovascular Toxicology, 1(4), 267-283.

Molecular mechanisms of cardiac hypertrophy induced by toxicants. / Chen, Qin; Tu, V. C.; Purdon, S.; Wood, J.; Dilley, T.

In: Cardiovascular Toxicology, Vol. 1, No. 4, 2001, p. 267-283.

Research output: Contribution to journalArticle

Chen, Q, Tu, VC, Purdon, S, Wood, J & Dilley, T 2001, 'Molecular mechanisms of cardiac hypertrophy induced by toxicants.', Cardiovascular Toxicology, vol. 1, no. 4, pp. 267-283.
Chen, Qin ; Tu, V. C. ; Purdon, S. ; Wood, J. ; Dilley, T. / Molecular mechanisms of cardiac hypertrophy induced by toxicants. In: Cardiovascular Toxicology. 2001 ; Vol. 1, No. 4. pp. 267-283.
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