Abstract
Nitro-conjugated linoleic acid (NO(2)-CLA) is formed by metabolic and inflammatory reactions of nitric oxide and nitrite, and represents the most abundant nitro-fatty acid species in humans. These electrophilic fatty acid nitroalkene derivatives mediate pleiotropic cell signaling responses. Here, we report a systematic approach to investigate the effect of NO(2)-CLA on human coronary artery smooth muscle cells (hCASMC), based on the RNA-Seq and bioinformatics analysis. There were extensive differentially expressed genes in NO(2)-CLA vs. control (510) and NO(2)-CLA vs. CLA (272) treatment groups, respectively. Notably, only minimal alterations were observed in CLA vs. control conditions, indicating that the electrophilic character of NO(2)-CLA is requited to induce differential gene expression responses independently from native CLA. Functional enrichment analysis of differentially expressed genes reveals multiple cellular processes to be affected under NO(2)-CLA treatment, including cell proliferation, lipid metabolism, antioxidant and inflammatory-related gene expression responses. These findings reveal that nitro-fatty acid derivatives such as NO(2)-CLA regulate a broad array of adaptive gene expression responses by hCASMC.