Oxidative burden in familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein cholesterol (LDL-c). FH is characterized by accelerated development of atherosclerosis and represents the most frequent hereditary cause of premature coronary heart disease. Mutations of the LDL receptor gene are the genetic signature of FH, resulting in abnormal levels of circulating LDLs. Moreover, FH promotes the generation of reactive oxygen species (ROS) which is another key mechanism involved in atherosclerosis development and progression. The aim of this narrative review is to update the current knowledge on the pathophysiological mechanisms linking FH to ROS generation and their detrimental impact on atherosclerotic pathophysiology. With this purpose, we reviewed experimental and clinical data on the association between FH and OS and the functional role of OS as a promoter of inflammation and atherosclerosis. In this regard, oxidant species such as oxidized LDL, malondialdehyde, ROS and isoprostanes emerged as leading mediators of the oxidative injury in FH. In conclusion, targeting oxidative stress may be a promising therapeutic strategy to reduce atherogenesis in patients with FH.