Lysophosphatidylcholine enhances oxidative stress via the 5-lipoxygenase pathway in rat aorta during aging

Lysophosphatidylcholine (LPC) is a lysolipid, acting as a potent cellular mediator of various biological processes. The purpose of this study was to define the role of LPC as a possible causative factor of disrupted redox balance in aged aorta from rats. In this study, we found elevated serum LPC levels in 24-month-old rats that were correlated with the age-related increase in cytosolic phospholipase A(2) (PLA(2)) activity. We also found that aortas from old rats showed increased 5-lipoxygenase (5-LO) activity. With the LPC-treated endothelial cells (YPEN-1 cells), we observed a rapid generation of reactive species, leading to enhanced oxidative stress. Our further investigations using specific 5-LO inhibitors led to the identification of a 5-LO pathway as the reactive species production source in the LPC-treated cells. Additional validation of this 5-LO pathway was made by the detection of increased leukotriene B4 generation in the LPC-treated cells. These in vitro data supported findings of increased expression and activation of aortic 5-LO in old rats by LPC. Together, our data strongly suggested that LPC caused the enhancement of oxidative stress in aged aorta through reactive species generation by an activated 5-LO pathway. LPC may well be an important contributor to age-related oxidative stress in aging aorta.