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The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.

Publication ,  Journal Article
Stiber, JA; Wu, J-H; Zhang, L; Nepliouev, I; Zhang, Z-S; Bryson, VG; Brian, L; Bentley, RC; Gordon-Weeks, PR; Rosenberg, PB; Freedman, NJ
Published in: Arteriosclerosis, thrombosis, and vascular biology
May 2016

Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfamily C TRP (TRPC) channels requires the scaffolding protein Homer 1, which associates with the actin-binding protein Drebrin. We found that SMC Drebrin expression is upregulated in atherosclerosis and in response to injury and investigated whether Drebrin inhibits SMC activation, either through regulation of TRP channel function via Homer or through a direct effect on the actin cytoskeleton.Wild-type (WT) and congenic Dbn(-/+) mice were subjected to wire-mediated carotid endothelial denudation. Subsequent neointimal hyperplasia was 2.4±0.3-fold greater in Dbn(-/+) than in WT mice. Levels of globular actin were equivalent in Dbn(-/+) and WT SMCs, but there was a 2.4±0.5-fold decrease in filamentous actin in Dbn(-/+) SMCs compared with WT. Filamentous actin was restored to WT levels in Dbn(-/+) SMCs by adenoviral-mediated rescue expression of Drebrin. Compared with WT SMCs, Dbn(-/+) SMCs exhibited increased TRP channel activity in response to platelet-derived growth factor, increased migration assessed in Boyden chambers, and increased proliferation. Enhanced TRP channel activity and migration in Dbn(-/+) SMCs were normalized to WT levels by rescue expression of not only WT Drebrin but also a mutant Drebrin isoform that binds actin but fails to bind Homer.Drebrin reduces SMC activation through its interaction with the actin cytoskeleton but independently of its interaction with Homer scaffolds.

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Published In

Arteriosclerosis, thrombosis, and vascular biology

DOI

EISSN

1524-4636

ISSN

1079-5642

Publication Date

May 2016

Volume

36

Issue

5

Start / End Page

984 / 993

Related Subject Headings

  • Vascular Remodeling
  • Transient Receptor Potential Channels
  • Transfection
  • Signal Transduction
  • Protein Binding
  • Phenotype
  • Neuropeptides
  • Neointima
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
 

Citation

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Stiber, J. A., Wu, J.-H., Zhang, L., Nepliouev, I., Zhang, Z.-S., Bryson, V. G., … Freedman, N. J. (2016). The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia. Arteriosclerosis, Thrombosis, and Vascular Biology, 36(5), 984–993. https://doi.org/10.1161/atvbaha.115.306140
Stiber, Jonathan A., Jiao-Hui Wu, Lisheng Zhang, Igor Nepliouev, Zhu-Shan Zhang, Victoria G. Bryson, Leigh Brian, et al. “The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.Arteriosclerosis, Thrombosis, and Vascular Biology 36, no. 5 (May 2016): 984–93. https://doi.org/10.1161/atvbaha.115.306140.
Stiber JA, Wu J-H, Zhang L, Nepliouev I, Zhang Z-S, Bryson VG, et al. The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia. Arteriosclerosis, thrombosis, and vascular biology. 2016 May;36(5):984–93.
Stiber, Jonathan A., et al. “The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 36, no. 5, May 2016, pp. 984–93. Epmc, doi:10.1161/atvbaha.115.306140.
Stiber JA, Wu J-H, Zhang L, Nepliouev I, Zhang Z-S, Bryson VG, Brian L, Bentley RC, Gordon-Weeks PR, Rosenberg PB, Freedman NJ. The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia. Arteriosclerosis, thrombosis, and vascular biology. 2016 May;36(5):984–993.

Published In

Arteriosclerosis, thrombosis, and vascular biology

DOI

EISSN

1524-4636

ISSN

1079-5642

Publication Date

May 2016

Volume

36

Issue

5

Start / End Page

984 / 993

Related Subject Headings

  • Vascular Remodeling
  • Transient Receptor Potential Channels
  • Transfection
  • Signal Transduction
  • Protein Binding
  • Phenotype
  • Neuropeptides
  • Neointima
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular