12-Nitrolinoleate

12-Nitrolinoleate is a linoleic acid derivative that acts as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Formed via exposure to acidified nitrite, it is present in human red blood cells and plasma. This compound stimulates PPARγ-dependent gene expression, demonstrated in a reporter assay with MCF-7 cells expressing human PPARγ, with an EC50 of 0.045 µM. At 2.5 µM, 12-Nitrolinoleate reduces the secretion of IL-6, TNF-α, and chemokine (C-C motif) ligand 2 (CCL2) in THP-1 and RAW 264.7 macrophages, and it suppresses LPS-induced NF-κB transcriptional activity in RAW 264.7 macrophages. Additionally, it inhibits TNF-α-induced increases in vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and enhances heme oxygenase-1 (HO-1) levels in primary human aortic endothelial cells at concentrations of 1, 5, or 10 µM.