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Hypertension-Causing Mutation in Peroxisome Proliferator-Activated Receptor γ Impairs Nuclear Export of Nuclear Factor-κB p65 in Vascular Smooth Muscle.


ABSTRACT: Selective expression of dominant negative (DN) peroxisome proliferator-activated receptor γ (PPARγ) in vascular smooth muscle cells (SMC) results in hypertension, atherosclerosis, and increased nuclear factor-κB (NF-κB) target gene expression. Mesenteric SMC were cultured from mice designed to conditionally express wild-type (WT) or DN-PPARγ in response to Cre recombinase to determine how SMC PPARγ regulates expression of NF-κB target inflammatory genes. SMC-specific overexpression of WT-PPARγ or agonist-induced activation of endogenous PPARγ blunted tumor necrosis factor α (TNF-α)-induced NF-κB target gene expression and activity of an NF-κB-responsive promoter. TNF-α-induced gene expression responses were enhanced by DN-PPARγ in SMC. Although expression of NF-κB p65 was unchanged, nuclea

SUBMITTER: Mukohda M 

PROVIDER: S-EPMC5472224 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature