Nitro-oleic acid decreases transcription of the angiotensin II type I receptor gene in aortic smooth muscle cells

Abstract

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.