Targeting high-density lipoproteins: update on a promising therapy

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Pharmacology

Background:

• High density lipoproteins (HDL) are established as negative risk factors for cardiovascular disease.
• HDL's atheroprotective effects stem from reverse cholesterol transport and pleiotropic functions like anti-inflammatory and antioxidant properties.
• HDL-targeted therapies are a promising strategy against atherosclerosis and cardiovascular risk.

Purpose of the Study:

• To provide an overview of therapeutic strategies aimed at modulating HDL levels and functions.
• To discuss the challenges and recent failures in HDL-targeted therapies.
• To highlight the importance of targeting specific HDL functions over simply increasing HDL levels.

Main Methods:

• Review of epidemiological studies on HDL's role in atherosclerosis.
• Analysis of HDL's multiple atheroprotective mechanisms.
• Evaluation of recent clinical trial outcomes for HDL-targeting drugs.

Main Results:

• Clinical trials targeting HDL-cholesterol (HDL-C) levels have yielded disappointing results.
• Increasing HDL levels alone may not be sufficient to confer cardiovascular benefits.
• The heterogeneity of HDL functions complicates direct therapeutic targeting.

Conclusions:

• Future HDL-targeted therapies should focus on specific HDL functions rather than solely increasing HDL levels.
• Targeting the mechanisms underlying HDL's pleiotropic effects holds greater promise for cardiovascular risk reduction.
• Development of effective HDL-related therapies remains an unmet clinical need.