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Inhibition of Smooth Muscle Cell Proliferation and Migration by a Talin Modulator Attenuates Neointimal Formation after Femoral Arterial Injury

Korean Circulation Journal 2020년 50권 7호 p.613 ~ 624
Lim I-Rang, 김정호, Jung Jong-Wha, 김종호, 홍순준,
소속 상세정보
 ( Lim I-Rang ) - Korea University College of Medicine Department of Cardiology
김정호 ( Kim Chung-Ho ) - Korea University Department of Life Sciences
 ( Jung Jong-Wha ) - Kyungpook National University College of Pharmacy
김종호 ( Kim Jong-Ho ) - Korea University College of Medicine Department of Cardiology
홍순준 ( Hong Soon-Jun ) - Korea University College of Medicine Department of Cardiology

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.

키워드

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

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