Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Oxidized low-density lipoprotein (ox-LDL) is critical to atherosclerosis in hyperlipidemia. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are important in preventing atherosclerosis, however these cells are significantly decreased in number in hyperlipidemia. This study aimed to determine whether ox-LDL and hyperlipidemia exert similar effects on EPC populations, and to investigate the involvement of reactive oxygen species (ROS). ROS production in BM and blood was significantly increased in male C57BL/6 mice treated with intravenous ox-LDL, and in hyperlipidemic LDL receptor knockout mice fed with a 4-month high-fat diet. ROS formation was effectively blocked by overexpression of antioxidant enzymes or N-acetylcysteine treatment. In both hyperlipidemic and ox-LDL-treated mice, the number of c-Kit+/CD31+ cells in BM and blood and of Sca-1+/Flk-1+ cells in blood significantly decreased, whereas the number of blood CD34+/Flk-1+ cells increased. In contrast, the number of blood CD34+/CD133+ cells increased in ox-LDL-treated mice but decreased in hyperlipidemic mice. Only the changes in CD34+/Flk-1+ cell number were prevented by inhibiting ROS production. These data suggested that ox-LDL produced significant changes in BM and blood EPC populations, largely similar to chronic hyperlipidemia, via predominantly ROS-independent mechanism(s).