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Protein Isolation from the Developing Embryonic Mouse Heart Valve Region
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Protein Isolation from the Developing Embryonic Mouse Heart Valve Region

Published on: September 23, 2014

Notch1 represses osteogenic pathways in aortic valve cells

Vishal Nigam1, Deepak Srivastava

  • 1Gladstone Institute of Cardiovascular Disease and Departments of Pediatrics, University of California, San Francisco, CA 94158, USA. vnigam@ucsd.edu

Journal of Molecular and Cellular Cardiology
|August 22, 2009
PubMed

Insights

Notch1 signaling normally prevents aortic valve calcification. Its inhibition promotes osteoblast-like gene expression and calcification, mediated by bone morphogenic protein 2 (Bmp2).

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Genetics of Valvular Heart Disease

Background:

  • Calcific aortic stenosis is a prevalent cause of adult heart disease.
  • Molecular mechanisms underlying aortic valve calcification remain poorly understood.
  • NOTCH1 mutations are linked to bicuspid aortic valve and calcification.

Purpose of the Study:

  • To elucidate the mechanism by which NOTCH1 represses aortic valve calcification.
  • To investigate the role of Notch signaling in aortic valve interstitial cells (AVICs).

Main Methods:

  • Utilized heterozygous Notch1-null mice to assess in vivo calcification.
  • Inhibited Notch signaling in cultured sheep AVICs to evaluate calcification and gene expression.
  • Examined the effect of bone morphogenic protein 2 (Bmp2) on Notch inhibition-induced calcification.

Main Results:

  • Notch1-null mice exhibited significantly increased aortic valve calcification.
  • Notch inhibition in AVICs led to a fivefold increase in calcification and osteoblast-like gene expression.
  • Notch1 was found to repress Bmp2 expression in aortic valve cells.
  • Bmp2 knockdown abrogated calcification induced by Notch inhibition in AVICs.

Conclusions:

  • Notch1 signaling plays a crucial role in repressing osteoblast-like calcification pathways in aortic valves.
  • Bone morphogenic protein 2 (Bmp2) is a key mediator of Notch-dependent aortic valve calcification.

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