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Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular endothelial cells by steady laminar shear stress, a physiologic fluid mechanical stimulus. MAD-related proteins are a recently identified family of intracellular proteins that are thought to be essential components in the signaling pathways of the serine/threonine kinase receptors of the transforming growth factor beta superfamily. Smad6 and Smad7 possess unique structural features (compared with previously described MADs), and they can physically interact with each other, and, in the case of Smad6, with other known human MAD species, in endothelial cells. Transient expression of Smad6 or Smad7 in vascular endothelial cells inhibits the activation of a transfected reporter gene in response to both TGF-beta and fluid mechanical stimulation. Both Smad6 and Smad7 exhibit a selective pattern of expression in human vascular endothelium in vivo as detected by immunohistochemistry and in situ hybridization. Thus, Smad6 and Smad7 constitute a novel class of MAD-related proteins, termed vascular MADs, that are induced by fluid mechanical forces and can modulate gene expression in response to both humoral and biomechanical stimulation in vascular endothelium.

Pubmed ID: 9256479

Authors

  • Topper JN
  • Cai J
  • Qiu Y
  • Anderson KR
  • Xu YY
  • Deeds JD
  • Feeley R
  • Gimeno CJ
  • Woolf EA
  • Tayber O
  • Mays GG
  • Sampson BA
  • Schoen FJ
  • Gimbrone MA
  • Falb D

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 19, 1997

Associated Grants

  • Agency: NHLBI NIH HHS, Id: P50-HL56985
  • Agency: NHLBI NIH HHS, Id: R37-HL51150

Mesh Terms

  • Amino Acid Sequence
  • Cells, Cultured
  • DNA-Binding Proteins
  • Endothelium, Vascular
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Molecular Sequence Data
  • Sequence Alignment
  • Signal Transduction
  • Smad6 Protein
  • Smad7 Protein
  • Stress, Mechanical
  • Trans-Activators