Small Dense Low-Density Lipoprotein: Biomarker or Potential Drug Target?

Abstract

AbstractIschemic heart disease is currently an epidemic affecting individuals worldwide. Increased incidence along with earlier onset of disease has led to the constant search for biomarkers that will help in earlier identification and treatment of at risk individuals. Small dense low-density lipoprotein (sdLDL) is the atherogenic subtype of low-density lipoprotein (LDL). It is smaller in size and higher in density in comparison to other LDL subtypes. Higher levels of sdLDL have beenfound to be associated with increased incidence of ischemic heart disease and adverse outcomes. Properties including decreased resistance to oxidative stress and prolonged residence time in the circulation account for its increased atherogenic potential. Hence intervention approaches targeting sdLDL directly in at risk individuals may be beneficial.Genetic, lifestyle, and environmental factors affect sdLDL levels.But the main determining factor is the level of triglycerides (TGs). Higher TG levels are associated with higher levels of very low density lipoprotein (VLDL) 1 and sdLDL. Various drugs have been used for targeting sdLDL with varying outcomes; drugs tried out include statins, fibrates, niacin, cholesterol ester transfer protein inhibitors and sodium-glucose co-transporter-2 inhibitors. Future prospects include modification of enzymes involved in fatty acid and TG synthesis, for example, lipoprotein lipase and acyl CoA carboxylase. However, further research is still necessary to draw clear guidelines for sdLDL reduction therapy in coronary artery disease treatment and prevention.