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KMID : 1094720140190040740
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Biotechnology and Bioprocess Engineering
2014 Volume.19 No. 4 p.740 ~ p.746
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Nitro-oleic acid decreases transcription of the angiotensin II type I receptor gene in aortic smooth muscle cells
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Wang Huan
Ouyang Hongsheng
Tian Yaping
Li Zhuang
Han Xiaolei
Liu Xingxing
Ran Guangyao
Wang Gangqi
Pang Daxin
Tang Xiaochun
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Abstract
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Nitroalkene derivatives of nitro-oleic acid (OA-NO2) regulate pluripotent cell signaling in vivo under physiological and pathological conditions. Angiotensin II type 1 receptor (AT1R) plays an important role in the cardiovascular system. In this study, OA-NO2 reduced the AT1R mRNA level, specifically in primary smooth muscle cells, showing a 70% reduction in rat smooth muscle cells (RASMCs) and a 50% reduction in pig smooth muscle cells (PASMCs). These effects were not observed in CHO cells, which highly express AT1R. The AT1R mRNA decay rate was unchanged after OA-NO2 compared with OA treatment. Nitric oxide (NO) and peroxisome proliferator-activated receptor gamma (PPARγ) did not alter the reduced effects of OA-NO2 on the AT1R mRNA level in SMCs. However, Sp1-mediated activation of the AT1R promoter was reduced in response to OA-NO2 in RASMCs but not 293T cells. In addition, the nuclear factor-kappa B (NF-κB) pathway was involved in the OA-NO2-mediated downregulation of AT1R transcription in SMCs. Taken together, our results demonstrate that OA-NO2 specifically inhibits AT1R mRNA expression in primary smooth muscle cells via the NF-κB pathway.
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KEYWORD
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nitroalkenes, angiotensin II type 1 receptor, smooth muscle cells, transcriptional regulation
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