High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Immunology

Background:

• Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with atherosclerotic cardiovascular disease risk.
• Recent studies question the protective role of HDL, as increased HDL-C levels did not consistently reduce cardiovascular risk.
• A controversy exists regarding whether HDL-C levels reflect HDL function or its atheroprotective capacity.

Purpose of the Study:

• To investigate whether high-density lipoprotein (HDL) can promote atherosclerosis regression.
• To elucidate the mechanisms underlying HDL-mediated plaque regression.
• To reconcile the discrepancy between epidemiological observations and clinical trial outcomes regarding HDL-C and cardiovascular risk.

Main Methods:

• Review of preclinical and clinical evidence on HDL function in atherosclerosis.
• Analysis of studies investigating the impact of increased functional HDL levels on atherosclerotic plaques.
• Examination of changes in plaque composition and inflammatory state associated with HDL intervention.

Main Results:

• HDL can promote atherosclerosis regression when functional HDL levels are increased.
• Regression involves reduced plaque lipid and macrophage content.
• A decrease in the inflammatory state of atherosclerotic plaques is observed.

Conclusions:

• Functional HDL particles, not just plasma HDL-C levels, are key to promoting atherosclerosis regression.
• HDL-mediated plaque regression involves reduced lipid load, macrophage infiltration, and inflammation.
• Distinguishing between HDL function and HDL-C levels is crucial for understanding HDL's atheroprotective potential and guiding future cardiovascular therapies.