Reactive oxygen species and oxidized LDL generation processes (ROS/oxLDL generation)

The generation of reactive oxygen species (ROS) and the subsequent oxidative modification of low-density lipoprotein (LDL) are central processes in the pathogenesis of atherosclerosis (Steinberg, 1997, PubMed: 9154114). ROS, such as superoxide and hydrogen peroxide, are generated by enzymes like NADPH oxidase (NOX) and myeloperoxidase (MPO) within the vascular wall (Lambeth, 2004, PubMed: 15454750). These reactive species initiate lipid peroxidation and protein modification of LDL, resulting in oxidized LDL (oxLDL), which is highly pro-inflammatory and immunogenic. oxLDL is not recognized by the standard LDL receptor but is instead taken up by scavenger receptors (e.g., CD36, SR-A1) on macrophages, leading to foam cell formation and plaque development (Lusis, 2000, PubMed: 10972298). Pharmacological strategies targeting this process include the use of antioxidants like Vitamin E or probucol, and inhibitors of ROS-producing enzymes, although clinical success with general antioxidants has been limited (Stock et al., 2000, PubMed: 10898334).

Other names

Oxidative modification of LDLLipid peroxidation pathwayROS-mediated LDL oxidationoxLDL formation pathway

Inhibition of ROS-generating enzymes (e.g., NOX, MPO), scavenging of free radicals to prevent lipid peroxidation, and stabilization of LDL particles to resist oxidative damage (Steinberg, 1997, PubMed: 9154114).