Cytoplasmic signaling pathways that regulate cardiac hypertrophy

J. D. Molkentin, G. W. Dorn

Research output: Contribution to journalReview articlepeer-review

574 Scopus citations


This review discusses the rapidly progressing field of cardiomyocyte signal transduction and the regulation of the hypertrophic response. When stimulated by a wide array of neurohumoral factors or when faced with an increase in ventricular-wall tension, individual cardiomyocytes undergo hypertrophic growth as an adaptive response. However, sustained cardiac hypertrophy is a leading predictor of future heart failure. A growing number of intracellular signaling pathways have been characterized as important transducers of the hypertrophic response, including specific G protein isoforms, low-molecular-weight GTPases (Ras, RhoA, and Rac), mitogen-activated protein kinase cascades, protein kinase C, calcineurin, gp130-signal transducer and activator of transcription, insulin-like growth factor I receptor pathway, fibroblast growth factor and transforming growth factor β receptor pathways, and many others. Each of these signaling pathways has been implicated as a hypertrophic transducer, which collectively suggests an emerging paradigm whereby multiple pathways operate in concert to orchestrate a hypertrophic response.

Original languageEnglish
Pages (from-to)391-426
Number of pages36
JournalAnnual Review of Physiology
StatePublished - Apr 26 2001


  • Cardiomyocytes
  • Heart failure
  • Kinase
  • Phosphatase
  • Signaling


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