Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration

Decha Pinkaew, Sung Gook Cho, David Y. Hui, John E. Wiktorowicz, Nongporn Hutadilok-Towatana, Wilawan Mahabusarakam, Moltira Tonganunt, Lewis J. Stafford, Amornrat Phongdara, Mingyao Liu, Ken Fujise

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23 Scopus citations

Abstract

Background: In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon. Methods: In endothelium-denudated mouse carotid arteries, oral morelloflavone-an active ingredient of the Thai medicinal plant Garcinia dulcis-significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis. Results: These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest. General significance: We propose morelloflavone to be a viable oral agent for the prevention of restenosis, without compromising effects on the integrity and healing of the injured arteries.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Garcinia dulcis
  • Migration
  • Morelloflavone
  • Restenosis
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Pinkaew, D., Cho, S. G., Hui, D. Y., Wiktorowicz, J. E., Hutadilok-Towatana, N., Mahabusarakam, W., Tonganunt, M., Stafford, L. J., Phongdara, A., Liu, M., & Fujise, K. (2009). Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration. Biochimica et Biophysica Acta - General Subjects, 1790(1), 31-39. https://doi.org/10.1016/j.bbagen.2008.09.006