N-acetyl cysteine prevents ambient fine particulate matter-potentiated atherosclerosis via inhibition of reactive oxygen species-induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell

Ambient fine particulate matter (PM) serves an important role in the development of cardiovascular disease, including atherosclerosis. Antioxidant N-acetyl cysteine (NAC) has protective effects in the cardiovascular system. However, it is unknown if NAC prevents PM-potentiated atherosclerosis in hyperlipidemia. Low-density lipoprotein (LDL) receptor knockout mice were pretreated with 1 mg/ml NAC in drinking water for 1 week and continued to receive NAC, high-fat diet and intranasal instillation of PM for 1 week or 6 months. Blood plasma was collected for lipid profile, oxidized (ox-)LDL, blood reactive oxygen species (ROS) and inflammatory cytokine (TNF-alpha, IL-1 beta and IL-6) measurement. Blood cells were harvested for endothelial progenitor cell (EPC) population and intracellular ROS analysis. Murine aorta was isolated for atherosclerotic plaque ratio calculation. NAC treatment maintained circulating EPC level and significantly decreased blood ox-LDL and ROS, inflammatory cytokines, mononuclear and EPC intracellular ROS levels as well as aortic plaque ratio. NAC prevented PM-potentiated atherosclerosis by inhibiting plasma ROS-induced ox-LDL elevation, mononuclear cell and EPC intracellular ROS-induced circulating EPC reduction and inflammatory cytokine production.

Automated summary

The antioxidant N-acetyl cysteine (NAC) has been found to have protective effects against the development of atherosclerosis, particularly when potentiated by ambient fine particulate matter (PM) in individuals with hyperlipidemia. NAC treatment was shown to decrease levels of oxidized LDL, reactive oxygen species, and inflammatory cytokines in the blood, while maintaining circulating endothelial progenitor cells. These effects ultimately led to a reduction in atherosclerotic plaque formation, demonstrating the potential of NAC in preventing PM-potentiated atherosclerosis.