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Inhibitory effect of CP-25 on intimal formation and vascular hyperplasia via suppression of GRK2/ERK1/2/EVI1 signaling.
Zhang, Jing; Liu, Yang; Long, Ming; Li, Jun; Zhao, Weikun; Su, Qiang.
Afiliación
  • Zhang J; Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Guangxi Autonomous Region, People's Republic of China.
  • Liu Y; Department of Cardiology, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Guangxi Autonomous Region, People's Republic of China.
  • Long M; Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, People's Republic of China.
  • Li J; Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Guangxi Autonomous Region, People's Republic of China.
  • Zhao W; Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guangxi Autonomous Region, 541001, People's Republic of China.
  • Su Q; Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guangxi Autonomous Region, 541001, People's Republic of China. Electronic address: suqiang_med@126.com.
Arch Biochem Biophys ; 694: 108601, 2020 11 15.
Article en En | MEDLINE | ID: mdl-32980350
ABSTRACT
Excessive proliferation, migration and dedifferentiation of vascular smooth muscle cells (VSMCs) are the center of intimal formation during in-stent restenosis and vein graft disease. Paeoniflorin-6'-O-benzene sulfonate (CP-25) is known to suppress inflammation and atherogenesis. However, the potential effect of CP-25 on intimal formation remains elusive. In the present study, we found that CP-25 significantly attenuated wire injury-induced intimal formation in C57BL/6 mice (intimal area 2.64 ± 0.25 × 104 µm2 vs. 1.53 ± 0.21 × 104 µm2, P < 0.05) and vascular hyperplasia indicated by PCNA staining. In vitro experiments showed that CP-25 significantly alleviated human aortic smooth muscle cell (HASMC) proliferation, migration and dedifferentiation induced by PDGF-BB. Mechanistically, CP-25 inhibited GRK2 phosphorylation through PDGF receptor in the presence of PDGF-BB. In accordance with these results, CP-25 disrupted the interaction of GRK2 with ERK1/2 and suppressed the activation of ERK1/2 signaling in HASMCs. EVI1, which is considered as a downstream of ERK1/2 signaling and a novel transcription factor for VSMC differentiation, was also downregulated by CP-25 treatment. Moreover, overexpression of EVI1 partly restored the decreased proliferation and dedifferentiation of HASMCs treated by CP-25. Collectively, these findings suggested that CP-25 could alleviate intimal formation in response to wire injury via suppression of the interaction of GRK2 and ERK1/2 and EVI1 activation, indicating CP-25 might serve as a potent pharmaceutical for intimal formation.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sistema de Señalización de MAP Quinasas / Monoterpenos / Glucósidos / Hiperplasia Límite: Animals / Humans / Male Idioma: En Revista: Arch Biochem Biophys Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sistema de Señalización de MAP Quinasas / Monoterpenos / Glucósidos / Hiperplasia Límite: Animals / Humans / Male Idioma: En Revista: Arch Biochem Biophys Año: 2020 Tipo del documento: Article