Premium
Endoplasmic reticulum stress signaling modulates smooth muscle phenotypes
Author(s) -
Shen Hua,
Manabe Ichiro,
Eguchi Kosei,
Fujiu Katsuhito,
Nagai Ryozo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.744.2
Subject(s) - endoplasmic reticulum , unfolded protein response , proinflammatory cytokine , downregulation and upregulation , endocrinology , medicine , xbp1 , microbiology and biotechnology , vascular smooth muscle , biology , chemistry , inflammation , biochemistry , gene , rna , smooth muscle , rna splicing
Metabolic syndrome is a major risk factor for atherosclerotic cardiovascular disease. Increased circulating free fatty acid (FFA) levels have been suggested to directly contribute to insulin resistance. Moreover, FFAs and changes in their contents have been shown to be associated with higher risks for cardiovascular disease. However, little is known regarding effects of FFA on vascular cells. Endoplasmic reticulum (ER), in which proteins are synthesized and folded, is increasingly regarded as a major site that responds to various stress, such as cellular energy levels, redox state, and hypoxia. We found that palmitate, a major free fatty acid in plasma, elicited ER stress markers including Bip, spliced XBP, and CHOP in cultured vascular smooth muscle cells (SMCs). Moreover, infusion of palmitate induced ER stress response in aorta in mice. Palmitate treatment resulted in upregulation of KLF5, PDGF, MMP3, and MMP9, whose expression are characteristics to phenotypic modulated SMCs. The ER stress attenuator, tauroursodeoxycholate (TUDCA), suppressed ER stress response as well as the upregulation of the genes involved in phenotypic modulation. Taken together, palmitate induced phenotypic modulation and proinflammatory gene programs in SMCs. ER stress response signaling appears to play an important role in mediating proinflammatory signals in SMCs in metabolic syndrome.