The inhibition of the effect and mechanism of vascular intimal hyperplasia in Tiam1 knockout mice
Highlights: • Tiam1 was highly expressed in the neointimal layer of the ligated carotid artery. • The intimal hyperplasia in Tiam1 KO mice after the ligation decreased. • PDGF-induced proliferation of HASMCs were inhibited with Tiam1 knockdown. • Rac1 involved in the migration of HASMCs that Tiam1 promoted. 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{sup −/−} 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.