Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies

Matrix Biol. 2010 May;29(4):304-16. doi: 10.1016/j.matbio.2010.01.005. Epub 2010 Jan 22.


Here, we demonstrate that ADAMTS9, a highly conserved versican-degrading protease, is required for correct cardiovascular development and adult homeostasis. Analysis of Adamts9(+/LacZ) adult mice revealed anomalies in the aortic wall, valvulosinus and valve leaflets. Abnormal myocardial projections and 'spongy' myocardium consistent with non-compaction of the left ventricle were also found in Adamts9(+/LacZ) mice. During development, Adamts9 was expressed in derivatives of the Secondary Heart Field, vascular smooth muscle cells in the arterial wall, mesenchymal cells of the valves, and non-myocardial cells of the ventricles, but expression also continued in the adult heart and ascending aorta. Thus, the adult cardiovascular anomalies found in Adamts9(+/LacZ) hearts could result from subtle developmental alterations in extracellular matrix remodeling or defects in adult homeostasis. The valvular and aortic anomalies of Adamts9(+/LacZ) hearts were associated with accumulation of versican and a decrease in cleaved versican relative to WT littermates. These data suggest a potentially important role for ADAMTS9 cleavage of versican, or other, as yet undefined substrates in development and allostasis of cardiovascular extracellular matrix. In addition, these studies identify ADAMTS9 as a potential candidate gene for congenital cardiac anomalies. Mouse models of ADAMTS9 deficiency may be useful to study myxomatous valve degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAMTS9 Protein
  • Animals
  • Aorta / metabolism
  • Blood Vessels / metabolism
  • Cardiovascular System / metabolism
  • Embryonic Development / genetics
  • Embryonic Development / physiology*
  • Extracellular Matrix / metabolism
  • Genes
  • Heart / embryology*
  • Heart Defects, Congenital / metabolism
  • Heart Ventricles / metabolism
  • Lac Operon
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism
  • Versicans / metabolism*


  • Versicans
  • ADAM Proteins
  • ADAMTS9 Protein
  • ADAMTS9 protein, human