Oxidative burden in familial hypercholesterolemia

Area of Science:

• Cardiovascular Science
• Genetics
• Biochemistry

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder causing high LDL cholesterol (LDL-c).
• FH accelerates atherosclerosis and is a leading hereditary cause of premature coronary heart disease.
• Mutations in the LDL receptor gene are the hallmark of FH, leading to elevated circulating LDLs.

Purpose of the Study:

• To review the pathophysiological mechanisms linking FH to reactive oxygen species (ROS) generation.
• To update knowledge on the detrimental impact of ROS on atherosclerotic pathophysiology in FH.
• To examine the role of oxidative stress (OS) in FH-related inflammation and atherosclerosis.

Main Methods:

• Narrative review of experimental and clinical data.
• Analysis of the association between FH and OS.
• Evaluation of OS as a promoter of inflammation and atherosclerosis.

Main Results:

• FH promotes ROS generation, a key factor in atherosclerosis development.
• Oxidized LDL, malondialdehyde, ROS, and isoprostanes are key mediators of oxidative injury in FH.
• Oxidative stress plays a significant role in FH-related inflammation and atherogenesis.

Conclusions:

• Targeting oxidative stress presents a promising therapeutic strategy for reducing atherogenesis in FH patients.
• Understanding the link between FH, ROS, and atherosclerosis is crucial for developing new treatments.