The upregulation of α5β1 and αVβ3 integrins on blood vessels induced by the tumor necrosis factor-α( TNF-α) after cerebral ischemia

Objective To investigate the relationships between the upregulation of Tumor necrosis factor α( TNF-α),expression patterns of α5β1 and αVβ3 integrins on blood vessels and angiogenesis after cerebral ischemic stroke. Methods Brain ischemic tissue specimens were obtained from 13 patients with ischemic stroke,according to the time point after cerebral ischemic stroke,three groups were studied: 1 d,2 d and 4 d groups. And 5 normal brain tissue specimens were chosen for control subjects.ELISA was used to detect the expression of TNF-α),fibronectin( Fn),α5β1 and αVβ3 integrins in the cerebral ischemic brain.The brain endothelial cells( BECs) proliferation was assessed by performing dual-immunofluorescent staning( IF) for Ki67 and CD31 and the expression patterns of Fn,α5β1 and αVβ3 on blood vessels was assessed by performing dual-IF for CD31 / α5,CD31 / β3 and CD31 / Fn. Results The TNF-α in the ischemic brain increased at day 1,peaked at day 2,then declined at day 4.The contents of TNF-α at different time point were all significantly higher than that of the control brains( P 0. 01). The expression of α5β1 and αVβ3 integrins in the ischemic brain as well as the Fn,α5β1 and-αVβ3 on blood vessels was parallelly upregulated with time,and the expression of all the three markers at day 4 was significantly higher than that of the controls,which exactly coincided with the time course of BECs proliferation. Conclusions The early upregulation of TNF-α) after cerebral ischemia stroke promotes the angiogenesis by inducing the expression of α5β1 and αVβ3 on blood vessels.