Deletion of the FHL2 gene attenuates intima-media thickening in a partially ligated carotid artery ligated mouse model

Chi Yu Chen, Hsiao Ya Tsai, Shih Hung Tsai, Pao Hsien Chu, Po Hsun Huang, Jaw Wen Chen, Shing Jong Lin

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The four and a half LIM domain protein 2 (FHL2) is a member of the four and a half LIM domain (FHL) gene family, and it is associated with cholesterol-enriched diet-promoted atherosclerosis. However, the effect of FHL2 protein on vascular remodelling in response to hemodynamic alterations remains unclear. Here, we investigated the role of FHL2 in a model of restricted blood flow-induced atherosclerosis. To promote neointimal hyperplasia in vivo, we subjected FHL2+/+ and FHL2−/− mice to partial ligation of the left carotid artery (LCA). The expression of p-ERK and p-AKT was decreased in FHL2−/− mice. FHL2 bound to AKT regulated AKT phosphorylation and led to Rac1-GTP inactivation. FHL2 silencing in human aortic smooth muscle cells down-regulated the PDGF-induced phosphorylation of ERK and AKT. Furthermore, FHL2 silencing reduced cytoskeleton conformational changes and caused cell cycle arrest. We concluded that FHL2 is essential for the regulation of arterial smooth muscle cell function. FHL2 modulates proliferation and migration via mitogen-activated protein kinase (MAPK) and PI3K-AKT signalling, leading to arterial wall thickening and thus neointimal hyperplasia.

Original languageEnglish
Pages (from-to)160-173
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2020
Externally publishedYes

Keywords

  • carotid artery ligation
  • FHL2
  • neointimal hyperplasia
  • smooth muscle cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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