The inhibition of the effect and mechanism of vascular intimal hyperplasia in Tiam1 knockout mice

Biochem Biophys Res Commun. 2018 Feb 26;497(1):248-255. doi: 10.1016/j.bbrc.2018.02.065. Epub 2018 Feb 9.

Abstract

T-Cell Lymphoma Invasion and Metastasis 1 (Tiam1) is a specific nucleotide exchange factor (GEF) that can activate Rho-like GTPase and Rac1 and regulate various cellular processes, including cell cycle progression and cell migration. The roles of Tiam1 in vascular intimal hyperplasia, especially in vascular smooth muscle cell proliferation and migration, are not fully understood. In this study, we investigated the effect of Tiam1 on vascular intimal hyperplasia in a carotid artery ligation model and human aortic smooth muscle cells (HASMCs). We found that the expression of Tiam1 was up-regulated in the neointima of carotid artery ligation mice and that Tiam1-/- mice following carotid artery ligation had less neointimal formation compared with wild type mice. Knockdown of Tiam1 by siRNA markedly attenuated PDGF-induced migration and proliferation in HASMCs by inhibiting the activation of Rac1. Therefore, these results suggest that Tiam1 is an important regulator of intima hyperplasia. It may regulate vascular intimal hyperplasia through the activation of Rac1.

Keywords: Intimal hyperplasia; Smooth muscle cells; Tiam1; Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology*
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism
  • Tunica Intima / metabolism*
  • Tunica Intima / pathology*
  • Vascular Remodeling

Substances

  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tiam1 protein, mouse