Abstract
Increased levels of free fatty acid (FFA)-induced endothelial dysfunction play an important role in the initiation and development of atherosclerosis. Feprazone is a nonsteroidal anti-inflammatory compound. However, the beneficial effects of feprazone on FFA-induced endothelial dysfunction have not been reported before. In the current study, we found that treatment with feprazone ameliorated FFA-induced cell death of human aortic endothelial cells (HAECs) by restoring cell viability and reducing the release of lactate dehydrogenase (LDH). Importantly, we found that treatment with feprazone ameliorated FFA-induced oxidative stress by reducing the production of mitochondrial reactive oxygen species (ROS). In addition, feprazone prevented FFA-induced expression and secretion of proinflammatory cytokines and chemokines, such as chemokine ligand 5 (CCL5), interleukin-6 (IL-6), and interleukin-8 (IL-8). We also found that feprazone decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Interestingly, we found that feprazone reduced the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). Our results also demonstrate that feprazone prevented FFA-induced activation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. These findings suggest that feprazone might serve as a potential agent for the treatment of atherosclerosis by improving the endothelial function.