Regulation of cardiac cushion development by hyaluronan

T. D. Camenisch, J. Biesterfeldt, T. Brehm-Gibson, J. Bradley, J. A. McDonald

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Hyaluronan is an extracellular matrix component implicated in expansion of the extracellular space, organization of supramolecular architecture, cell motility, proliferation, tumour metastases and wound healing. Hyaluronan is highly expressed in the developing heart but it is only a minor component of the mature heart. The loss of hyaluronan synthase-2 (Has2) results in embryonic lethality with a phenotype remarkably similar to that of the versican-deficient heart defect mouse. Has2-deficient embryos lack hyaluronan-containing cardiac jelly, and at embryonic day 9.5 show arrested development, with an apparent absence of the right ventricle and underdevelopment of the conus-truncus segment, and pericardial effusion consistent with heart failure. Cardiac cushions are totally absent, and endocardial cell migration over collagen gels is not detectable in Has2-deficient atrioventricular (AV) canal explants. Endothelial to mesenchymal transformation is also defective in AV explants from Has2-null embryos. The normal phenotype is restored in AV canal explants from Has2-deficient embryos by co-culture with wild type AV canal explants, with conditioned media from wild type AV explants or with exogenous hyaluronan. These results provide evidence for a direct role for hyaluronan during endocardial cushion and AV canal morphogenesis.

Original languageEnglish (US)
Pages (from-to)4-10
Number of pages7
JournalExperimental and Clinical Cardiology
Volume6
Issue number1
StatePublished - Jan 1 2001

Keywords

  • Atrioventricular canal
  • Hyaluronan
  • Hyaluronan synthase-2
  • Morphogenesis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Camenisch, T. D., Biesterfeldt, J., Brehm-Gibson, T., Bradley, J., & McDonald, J. A. (2001). Regulation of cardiac cushion development by hyaluronan. Experimental and Clinical Cardiology, 6(1), 4-10.