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Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers.

Publication ,  Journal Article
Cho, H; Balaji, S; Sheikh, AQ; Hurley, JR; Tian, YF; Collier, JH; Crombleholme, TM; Narmoneva, DA
Published in: Acta biomaterialia
January 2012

RAD16-II peptide nanofibers are promising for vascular tissue engineering and were shown to enhance angiogenesis in vitro and in vivo, although the mechanism remains unknown. We hypothesized that the pro-angiogenic effect of RAD16-II results from low-affinity integrin-dependent interactions of microvascular endothelial cells (MVECs) with RAD motifs. Mouse MVECs were cultured on RAD16-II with or without integrin and MAPK/ERK pathway inhibitors, and angiogenic responses were quantified. The results were validated in vivo using a mouse diabetic wound healing model with impaired neovascularization. RAD16-II stimulated spontaneous capillary morphogenesis, and increased β(3) integrin phosphorylation and VEGF expression in MVECs. These responses were abrogated in the presence of β(3) and MAPK/ERK pathway inhibitors or on the control peptide without RAD motifs. Wide-spectrum integrin inhibitor echistatin completely abolished RAD16-II-mediated capillary morphogenesis in vitro and neovascularization and VEGF expression in the wound in vivo. The addition of the RGD motif to RAD16-II did not change nanofiber architecture or mechanical properties, but resulted in significant decrease in capillary morphogenesis. Overall, these results suggest that low-affinity non-specific interactions between cells and RAD motifs can trigger angiogenic responses via phosphorylation of β(3) integrin and MAPK/ERK pathway, indicating that low-affinity sequences can be used to functionalize biocompatible materials for the regulation of cell migration and angiogenesis, thus expanding the current pool of available motifs that can be used for such functionalization. Incorporation of RAD or similar motifs into protein engineered or hybrid peptide scaffolds may represent a novel strategy for vascular tissue engineering and will further enhance design opportunities for new scaffold materials.

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Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

January 2012

Volume

8

Issue

1

Start / End Page

154 / 164

Related Subject Headings

  • Wound Healing
  • Vascular Endothelial Growth Factor A
  • Tissue Scaffolds
  • Tissue Engineering
  • Oligopeptides
  • Neovascularization, Physiologic
  • Nanofibers
  • Mitogen-Activated Protein Kinases
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Cho, H., Balaji, S., Sheikh, A. Q., Hurley, J. R., Tian, Y. F., Collier, J. H., … Narmoneva, D. A. (2012). Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers. Acta Biomaterialia, 8(1), 154–164. https://doi.org/10.1016/j.actbio.2011.08.029
Cho, Hongkwan, Swathi Balaji, Abdul Q. Sheikh, Jennifer R. Hurley, Ye F. Tian, Joel H. Collier, Timothy M. Crombleholme, and Daria A. Narmoneva. “Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers.Acta Biomaterialia 8, no. 1 (January 2012): 154–64. https://doi.org/10.1016/j.actbio.2011.08.029.
Cho H, Balaji S, Sheikh AQ, Hurley JR, Tian YF, Collier JH, et al. Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers. Acta biomaterialia. 2012 Jan;8(1):154–64.
Cho, Hongkwan, et al. “Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers.Acta Biomaterialia, vol. 8, no. 1, Jan. 2012, pp. 154–64. Epmc, doi:10.1016/j.actbio.2011.08.029.
Cho H, Balaji S, Sheikh AQ, Hurley JR, Tian YF, Collier JH, Crombleholme TM, Narmoneva DA. Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers. Acta biomaterialia. 2012 Jan;8(1):154–164.
Journal cover image

Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

January 2012

Volume

8

Issue

1

Start / End Page

154 / 164

Related Subject Headings

  • Wound Healing
  • Vascular Endothelial Growth Factor A
  • Tissue Scaffolds
  • Tissue Engineering
  • Oligopeptides
  • Neovascularization, Physiologic
  • Nanofibers
  • Mitogen-Activated Protein Kinases
  • Mice, Inbred C57BL
  • Mice