High-density lipoproteins (HDL): Novel function and therapeutic applications

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Biochemistry

Background:

• High-density lipoprotein (HDL) raising agents have failed to reduce cardiovascular disease (CVD).
• Extremely high HDL-cholesterol levels are associated with increased cardiovascular mortality.
• Existing views on HDL function need re-evaluation.

Purpose of the Study:

• To explore the expanded role of HDL in lipolysis of triglyceride-rich lipoproteins (TGRLs).
• To investigate the reverse remnant-cholesterol transport (RRT) hypothesis.
• To identify novel therapeutic applications of HDL function in cardiovascular disease.

Main Methods:

• Investigated HDL's role in lipoprotein lipase-mediated TGRL lipolysis.
• Examined the mechanism of HDL acquiring surface lipids during TGRL lipolysis.
• Assessed the impact of HDL-mediated cholesterol transport on arterial wall cholesterol influx.

Main Results:

• HDL critically contributes to TGRL lipolysis by acquiring released surface lipids, including free cholesterol.
• This process facilitates the removal of atherogenic, cholesterol-rich TGRL remnants from circulation.
• HDL-mediated cholesterol transport to the liver for biliary excretion reduces arterial cholesterol deposition.

Conclusions:

• HDL's function extends beyond traditional roles, encompassing a critical part in TGRL lipolysis.
• The reverse remnant-cholesterol transport (RRT) hypothesis provides a new framework for understanding HDL's cardioprotective effects.
• Activating HDL-mediated cholesterol flux via lipolysis presents a promising therapeutic avenue for reducing CVD, particularly in statin-treated patients.