Beyond High-density Lipoprotein-cholesterol: Unraveling the Complexity of High-density Lipoprotein Functionality

Area of Science:

• Cardiovascular Biology
• Lipid Metabolism
• Molecular Medicine

Background:

• High-density lipoprotein (HDL) cholesterol (HDL-C) is traditionally linked to cardiovascular disease (CVD) risk.
• Recent evidence questions the sole reliance on HDL-C, emphasizing HDL functionality.
• HDL possesses diverse functions beyond cholesterol transport, including vasoprotective, anti-inflammatory, and antithrombotic roles.

Purpose of the Study:

• To explore the multifaceted functions of HDL beyond its cholesterol content.
• To highlight the limitations of current clinical assessments of HDL.
• To underscore the need for a comprehensive understanding of HDL's pleiotropic effects.

Main Methods:

• Review of recent scientific literature on HDL function.
• Analysis of key molecular pathways involved in HDL's actions, including reverse cholesterol transport (RCT).
• Examination of novel regulatory factors influencing HDL activity.

Main Results:

• HDL quantity (HDL-C) does not always correlate with HDL's functional capacity, such as RCT efficiency.
• HDL exerts vasoprotective, anti-inflammatory, and antithrombotic effects through various mechanisms.
• Emerging roles for HDL in the central nervous system suggest broader therapeutic potential.

Conclusions:

• A comprehensive understanding of HDL's diverse functions is crucial for both basic research and clinical practice.
• Current clinical assessments focusing primarily on HDL-C are insufficient.
• Further research into HDL's pleiotropic roles may unlock new therapeutic strategies for CVD and other conditions.