Inhibition of smooth muscle cell proliferation and migration by a talin modulator attenuates neointimal formation after femoral arterial injury

I. Rang Lim, Chungho Kim, Jong Wha Jung, Jong Ho Kim, Soon Jun Hong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Objectives: Vascular smooth muscle cell (SMC) proliferation and migration play a critical role in neointimal formation. Focal adhesion is involved in cell proliferation and migration, and talin is known to be a key regulator of these processes. We synthesized a new talin modulator that binds to the talin protein, and investigated its effects on SMCs and neointimal formation after vascular injury. Methods: Human aortic SMCs (HAoSMCs) were treated with a newly synthesized talin modulator. Apolipoprotein E knockout (ApoE KO) mice were subjected to left femoral arterial injury and orally administered with the talin modulator daily. Laser Doppler imager was used to compare the blood flow, and injured femoral arteries and blood serum were analyzed after 28 days. Results: The talin modulator significantly inhibited cell proliferation in a concentration-dependent manner and suppressed the migration of HAoSMCs. Treatment with a talin modulator resulted in a significant reduction in the phosphorylation of focal adhesion molecules and downstream signaling molecules related to cell proliferation and migration. The effects of the talin modulator in HAoSMCs were found to be reversible, as evidenced by the reactivation of signaling pathways upon its removal. After 28 days of administration of the talin modulator, an improvement in the blood flow and reduction in neointimal formation in the injured femoral arteries were observed. Conclusions: We demonstrated the inhibitory effects of a talin modulator on SMC proliferation and migration, and that were associated with downregulation of signaling pathways, resulting in the attenuation of neointimal formation in ApoE KO mice.

Original languageEnglish
Pages (from-to)613-624
Number of pages12
JournalKorean Circulation Journal
Volume50
Issue number7
DOIs
Publication statusPublished - 2020 Jul

Keywords

  • Focal adhesion
  • Neointima formation
  • Talin
  • Vascular injury
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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