Load induction of cardiac hypertrophy

George Cooper IV, Robert L. Kent, Douglas L. Mann

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We have shown in surgical animal models that increased and decreased cardiac loading results in myocardial hypertrophy and atrophy, respectively. These changes, which are readily reversible upon the restoration of a normal cardiac load, occur without any requirement for neural or circulating intermediary factors. In our current studies we have focused first on an unequivocal demonstration of these same phenomena in a much simpler model consisting of isolated quiescent cardiocytes maintained in serum-free medium and second on an elucidation in isolated papillary muscles of the means by which a change in cardiac load is transduced into a change in cardiac mass. Adherent isolated adult cardiocytes held at their rest length exhibit only a very gradual loss of their differentiated features. In contrast, unloaded cardiocytes in suspension culture immediately cease nuclear RNA synthesis and rapidly come to resemble unloaded cardiac muscle-a cardiocyte cellular analog of cardiac tissue atrophy, while loaded adherent cardiocytes stretched past their rest length respond in terms of synthetic activity characteristic of growth initiation-a cardiocyte cellular analog of cardiac tissue hypertrophy. Both quiescent and contracting papillary muscles exhibit increased synthesis of cardiocyte structural proteins in direct relation to active and/or passive muscle tension. This load-dependent protein synthesis appears to require initial sodium influx through deformation-dependent sarcolemmal cation channels, in a manner analogous to the dependence of mitogen-stimulated growth initiation in a variety of other cell types on initial sodium entry, albeit by a different mechanism. Thus, load variation functions as an independent regulator of cardiac growth in the adult, and sarcolemmal deformation with consequent sodium entry may be an initial direct link between load and growth in the heart.

Original languageEnglish
Pages (from-to)11-30
Number of pages20
JournalJournal of Molecular and Cellular Cardiology
Volume21
Issue numberSUPPL. 5
DOIs
StatePublished - Dec 1989
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • Cardiocyte
  • Load regulation
  • Papillary muscle
  • Sodium

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