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TNF-alpha regulates vascular smooth muscle cell responses in genetic hypertension.

Abstract：

:Cellular and molecular events in vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were investigated. SHR-derived VSMC showed increased proliferative capacity and MAP kinase levels in comparison with WKY-derived VSMC. Flow cytometry analysis revealed that progression from G1 to S phase was faster in SHR-derived VSMC in response to tumor necrosis factor-alpha (TNF-alpha) as compared with cells from WKY. The G1 cell cycle-associated proteins such as cyclin D1, cyclin E, CDK2 and CDK4, and kinase activities associated with CDK2 and CDK4, were increased in SHR-derived VSMC. In addition, CDK inhibitor p21 was elevated in SHR-derived cells. Matrix metalloproteinase-9 (MMP-9) expression and migration were also increased in response to TNF-alpha in SHR-derived cells. This increase was characterized by the up-regulation of MMP-9, which was transcriptionally regulated at the AP-1 and NF-kappaB sites in the MMP-9 promoter. These results suggest that the hypertensive-associated increase in VSMC proliferative capacity, G1 to S-phase cell-cycle progress and MMP-9 expression may play a role in vascular remodeling in hypertension.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Lee SJ,Kim WJ,Moon SK

doi

10.1016/j.intimp.2009.03.010

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

837-43

issue

7-8

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(09)00099-X

journal_volume

9

pub_type

杂志文章

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