Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia

Deron J. Tessier, Padmini Komalavilas, Bo Liu, Craig K. Kent, Jeffrey S. Thresher, Catherine M. Dreiza, Alyssa Panitch, Lokesh Joshi, Elizabeth Furnish, William Stone, Richard Fowl, Colleen M. Brophy

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Abstract

Background Human saphenous vein (HSV) is the autologous conduit of choice for peripheral vascular reconstructions. However, vasospasm can lead to early graft failure. The leading cause of delayed graft failure is intimal hyperplasia. Objective To develop a proteomic approach to prevent vein-graft spasm and intimal hyperplasia. Methods Biomimetic peptide analogs of the small heat shock-related protein HSP20, containing a protein transduction domain (PTD), a phosphorylated serine, and a sequence of HSP20 surrounding the phosphorylation site (PTD-pHSP20), or a scrambled sequence of the same amino acids surrounding the phosphorylation site (PTD-scHSP20) were synthesized. The peptides were used in muscle bath and organ culture experiments with human saphenous vein (HSV) segments. Cultured smooth muscle cell lines were used to determine the effect of the peptides on proliferation and migration. Results In HSV rings precontracted with norepinephrine, PTD-pHSP20 but not PTD-scHSP20 led to relaxation. There was no significant difference in smooth muscle cell proliferation in cells treated with PTD-pHSP20 compared with PTD-scHSP20. Treatment with PTD-pHSP20 significantly inhibited cellular migration compared with PTD-scHSP20. Control, untreated, and PTD-scHSP20-treated saphenous veins had significant increases in intimal thickness after culture. This intimal thickening was completely inhibited by treatment with PTD-pHSP20. Conclusions Protein transduction of biologically active motifs of HSP20 can affect pathologic and physiologic responses of HSV and represents a novel proteomic-based therapeutic approach.

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalJournal of Vascular Surgery
Volume40
Issue number1
DOIs
StatePublished - Jul 2004

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Tunica Intima
Small Heat-Shock Proteins
Hyperplasia
Peptides
Saphenous Vein
Transplants
Proteomics
Smooth Muscle Myocytes
Protein Domains
Phosphorylation
Biomimetics
Organ Culture Techniques
Spasm
Baths
Serine
Blood Vessels
Amino Acid Sequence
Veins
Norepinephrine
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Tessier, D. J., Komalavilas, P., Liu, B., Kent, C. K., Thresher, J. S., Dreiza, C. M., ... Brophy, C. M. (2004). Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia. Journal of Vascular Surgery, 40(1), 106-114. https://doi.org/10.1016/j.jvs.2004.03.028

Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia. / Tessier, Deron J.; Komalavilas, Padmini; Liu, Bo; Kent, Craig K.; Thresher, Jeffrey S.; Dreiza, Catherine M.; Panitch, Alyssa; Joshi, Lokesh; Furnish, Elizabeth; Stone, William; Fowl, Richard; Brophy, Colleen M.

In: Journal of Vascular Surgery, Vol. 40, No. 1, 07.2004, p. 106-114.

Research output: Contribution to journalArticle

Tessier, DJ, Komalavilas, P, Liu, B, Kent, CK, Thresher, JS, Dreiza, CM, Panitch, A, Joshi, L, Furnish, E, Stone, W, Fowl, R & Brophy, CM 2004, 'Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia', Journal of Vascular Surgery, vol. 40, no. 1, pp. 106-114. https://doi.org/10.1016/j.jvs.2004.03.028
Tessier, Deron J. ; Komalavilas, Padmini ; Liu, Bo ; Kent, Craig K. ; Thresher, Jeffrey S. ; Dreiza, Catherine M. ; Panitch, Alyssa ; Joshi, Lokesh ; Furnish, Elizabeth ; Stone, William ; Fowl, Richard ; Brophy, Colleen M. / Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia. In: Journal of Vascular Surgery. 2004 ; Vol. 40, No. 1. pp. 106-114.
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abstract = "Background Human saphenous vein (HSV) is the autologous conduit of choice for peripheral vascular reconstructions. However, vasospasm can lead to early graft failure. The leading cause of delayed graft failure is intimal hyperplasia. Objective To develop a proteomic approach to prevent vein-graft spasm and intimal hyperplasia. Methods Biomimetic peptide analogs of the small heat shock-related protein HSP20, containing a protein transduction domain (PTD), a phosphorylated serine, and a sequence of HSP20 surrounding the phosphorylation site (PTD-pHSP20), or a scrambled sequence of the same amino acids surrounding the phosphorylation site (PTD-scHSP20) were synthesized. The peptides were used in muscle bath and organ culture experiments with human saphenous vein (HSV) segments. Cultured smooth muscle cell lines were used to determine the effect of the peptides on proliferation and migration. Results In HSV rings precontracted with norepinephrine, PTD-pHSP20 but not PTD-scHSP20 led to relaxation. There was no significant difference in smooth muscle cell proliferation in cells treated with PTD-pHSP20 compared with PTD-scHSP20. Treatment with PTD-pHSP20 significantly inhibited cellular migration compared with PTD-scHSP20. Control, untreated, and PTD-scHSP20-treated saphenous veins had significant increases in intimal thickness after culture. This intimal thickening was completely inhibited by treatment with PTD-pHSP20. Conclusions Protein transduction of biologically active motifs of HSP20 can affect pathologic and physiologic responses of HSV and represents a novel proteomic-based therapeutic approach.",
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AU - Liu, Bo

AU - Kent, Craig K.

AU - Thresher, Jeffrey S.

AU - Dreiza, Catherine M.

AU - Panitch, Alyssa

AU - Joshi, Lokesh

AU - Furnish, Elizabeth

AU - Stone, William

AU - Fowl, Richard

AU - Brophy, Colleen M.

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N2 - Background Human saphenous vein (HSV) is the autologous conduit of choice for peripheral vascular reconstructions. However, vasospasm can lead to early graft failure. The leading cause of delayed graft failure is intimal hyperplasia. Objective To develop a proteomic approach to prevent vein-graft spasm and intimal hyperplasia. Methods Biomimetic peptide analogs of the small heat shock-related protein HSP20, containing a protein transduction domain (PTD), a phosphorylated serine, and a sequence of HSP20 surrounding the phosphorylation site (PTD-pHSP20), or a scrambled sequence of the same amino acids surrounding the phosphorylation site (PTD-scHSP20) were synthesized. The peptides were used in muscle bath and organ culture experiments with human saphenous vein (HSV) segments. Cultured smooth muscle cell lines were used to determine the effect of the peptides on proliferation and migration. Results In HSV rings precontracted with norepinephrine, PTD-pHSP20 but not PTD-scHSP20 led to relaxation. There was no significant difference in smooth muscle cell proliferation in cells treated with PTD-pHSP20 compared with PTD-scHSP20. Treatment with PTD-pHSP20 significantly inhibited cellular migration compared with PTD-scHSP20. Control, untreated, and PTD-scHSP20-treated saphenous veins had significant increases in intimal thickness after culture. This intimal thickening was completely inhibited by treatment with PTD-pHSP20. Conclusions Protein transduction of biologically active motifs of HSP20 can affect pathologic and physiologic responses of HSV and represents a novel proteomic-based therapeutic approach.

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